Administrative Appointments

  • Deputy Director, Canary Center at Stanford (2008 - 2009)

Boards, Advisory Committees, Professional Organizations

  • Member, Metastasis Research Society (2015 - Present)
  • Member, International Bone & Mineral Society (2013 - Present)
  • Associate Member, Stanford Cancer Institute (2012 - Present)
  • Member, American Association for Cancer Research (AACR) - Tumor Microenvironment Working Group (2009 - Present)
  • Associate Member, NIH/NCI EDRN (Early Detection Research Network) (2003 - Present)
  • Member, Yale Cancer Center (1993 - 2004)

Professional Education

  • PhD, U.C. Berkeley, Endocrinology
  • Teaching Credential, San Francisco State University, Biology
  • AB, U.C. Berkeley, Physiology

Research & Scholarship

Current Research and Scholarly Interests

My areas of interest are mammary gland biology and translational breast cancer research. I recently joined the Contag lab as an NIH Career Re-Entry Scientist, where I am using molecular imaging tools to study the process of cancer cell dissemination during breast cancer progression. We are currently using a human bone tissue model to study breast cancer cell colonization of the bone metastatic niche.



All Publications

  • Detection of non-melanoma skin cancer by in vivo fluorescence imaging with fluorocoxib probe. Neoplasia. Ra, H., Gonzalez-Gonzalez, E., Uddin, M., King, B., Lee, A., Ali-Kahn, I., Marnett, L., Tang, J., Contag, C. 2015; 17 (2): 201-207
  • Methods for Culturing Human Femur Tissue Explants to Study Breast Cancer Cell Colonization of the Metastatic Niche. J. Vis. Exp. Templeton, Z., Bachmann, M., Alluri, R., Maloney, W., Contag, C., King, B. 2015; 97: 1-10

    View details for DOI 10.3791/52656

  • Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Niche Neoplasia Templeton, Z. S., Lie, W., Wang, W., Rosenberg-Hasson, Y., Alluri, R. V., Tamaresis, J. S., Bachmann, M. H., Lee, K., Maloney, W. J., Contag, C. H., King, B. L. 2015; 17 (12): 849-861
  • Monitoring Dynamic Interactions Between Breast Cancer Cells and Human Bone Tissue in a Co-culture Model Molecular Imaging and Biology Contag, C. H., Lie, W., Bammer, M. C., Hardy, J. W., Schmidt, T. L., Maloney, W. J., King, B. L. 2014; 16 (2): 158-166
  • Multmodality optical imaging in diagnosis. Research in Translational Biophotonics: Four Case Studies Rogalla, S., Sensarn, S., King, B. L., Schmidt, T. L., Ra, H., Garai, E., Rimm, D., Ostrov, D., Uddin, M., Marnett, L., Zavaleta, C., Gambhir, S. S., Crawford, J., Van Dam, J., Friedland, S., Solgaard, O., Mandella, M., Contag, C. edited by Nordstrom, R. J. SPIE Press, Bellingham, WA. 2014: 243-285
  • AQUA and FISH analysis of HER-2/neu expression and amplification in a small cell lung carcinoma tissue microarray HISTOPATHOLOGY Giltnane, J. M., Murren, J. R., Rimm, D. L., King, B. L. 2006; 49 (2): 161-169


    Most small cell lung carcinoma (SCLC) patients have metastatic disease at the time of diagnosis and are faced with poor prognosis and limited treatment options. Reports of HER-2/neu gene amplification and overexpression in this malignancy have raised the possibility of applying targeted immunotherapy with trastuzumab, the monoclonal antibody used to treat metastatic breast cancer. However, a review of the studies measuring HER-2/neu gene amplification and protein expression in SCLC reveals discordant results. The aim of the present study was to re-examine HER-2/neu expression in SCLC in relation to gene copy number using the new, highly sensitive, immunofluorescence automated quantitative analysis (AQUA) technology.Fluorescence in situ hybridization (FISH) was used to measure HER-2/neu gene copy number and amplification status and AQUA was used to measure protein expression in a series of 23 SCLC tumours on a tissue microarray. None of the 17 SCLC specimens assessable by FISH exhibited HER-2/neu gene amplification as defined by a HER-2/neu/chromosome 17 ratio = or > 2. Twelve of 17 (70.1%) SCLC samples were polysomic for chromosome 17 with corresponding increases in HER-2/neu gene copy numbers. Intermediate levels of protein expression corresponding to AQUA scores in the range of 4-24 were detected in all 23 specimens. High protein expression levels corresponding to AQUA scores up to 83, observed previously in association with gene amplification and poor prognosis in breast cancer cases, were not detected in the present study. No statistically significant association was observed between absolute chromosome 17 or HER-2/neu gene copy numbers and protein expression levels in tumour cells (P > 0.45).The lack of gene amplification and robust HER-2/neu protein expression in SCLC tumour cells in this series does not suggest a prominent role for the HER-2/neu gene in SCLC tumour progression and does not support the general applicability of targeted immunotherapy with trastuzumab to this malignancy.

    View details for DOI 10.1111/j.1365-2559.2006.02479.x

    View details for Web of Science ID 000239119000006

    View details for PubMedID 16879393

  • The intraductal approach to the breast: raison d'etre Breast Cancer Research King, B. L., Love, S. M. 2006; 8 (2): 206-210
  • The Fourth International Symposium on the Intraductal Approach to Breast Cancer, Santa Barbara, California, 10-13 March 2005. King, B. L., Love, S. M., Rochman, S., Kim, J. A. 2005: 198-204


    Intraductal approaches encompass procedures and technologies that are designed to access and interrogate the ductal-alveolar systems of the human breast, and include nipple aspiration, ductal lavage, random periareolar fine needle aspiration, and ductoscopy. These approaches are being used to collect and analyze fluids and cells to develop methods for breast cancer detection and risk assessment; to introduce imaging technologies to explore the mammary tree for abnormalities; to administer therapeutic and/or preventive agents directly to the breast tissue; and to explore the biology of the normal mammary gland. The latest research findings in these areas, presented at The 4th International Symposium on the Intraductal Approach to Breast Cancer in 2005, are summarized in this report.

    View details for PubMedID 16168138

  • Patterns of reduced nipple aspirate fluid production and ductal lavage cellularity in women at high risk for breast cancer BREAST CANCER RESEARCH Higgins, S. A., Matloff, E. T., Rimm, D. L., Dziura, J., Haffty, B. G., King, B. L. 2005; 7 (6): R1017-R1022


    Nipple aspiration is a noninvasive technique for obtaining breast fluids from the duct openings of the nipple for the evaluation of abnormalities associated with breast cancer. Nipple aspirate fluid (NAF) can be elicited from 48 to 94% of healthy women, and its production has been linked to an increased relative risk for breast cancer development. NAF production has been used in studies to guide the selection of ducts for ductal lavage, a procedure in which ducts are cannulated and flushed with saline to collect cells. In a previous multicenter trial to evaluate intraductal approaches in women at high-risk for breast cancer, NAF production was observed in 84% of the subjects. However, we observed a significantly lower proportion of fluid-yielding subjects in a similar series of high-risk women. The purpose of the present study was to identify variables associated with this reduction.Nipple aspiration was performed on 33 high-risk women (defined as having a 5-year Gail model index of more than 1.7, a personal or family history of breast cancer, and/or a BRCA1 or BRCA2 germline mutation) to identify ductal orifices for lavage procedures. Lavage was performed on all fluid-yielding ducts and on nine non-fluid-yielding ducts.Fluid-yielding ducts were identified in 12 of 33 (36%) of the subjects in the present series, compared with 16 of 19 (84%) of the subjects undergoing identical procedures at our facility during a multicenter trial (P = 0.001). Reduced NAF yields were associated with postmenopausal status (P = 0.02), BRCA germline mutations (P = 0.004), and risk reduction therapies, including bilateral salpingo-oophorectomy (BSO) and/or selective estrogen receptor modulators (SERMs; P = 0.009). All nine (100%) of the ductal lavage specimens collected from non-fluidyielding ducts were acellular, in comparison with 3 of 13 specimens from fluid-yielding ducts (P < .001).Analysis of high-risk women in the present series revealed patterns of reduced NAF production and ductal lavage cellularity compared with a previous multicenter trial. The present series included more BRCA-positive women, many of whom had undergone BSO and/or were using SERMs. Our data suggest that endocrine mechanisms associated with these risk-reducing therapies may be related to patterns of diminished breast fluid production.

    View details for DOI 10.1186/bcr1335

    View details for Web of Science ID 000233956900028

    View details for PubMedID 16280052

  • Molecular markers for prognosis after isolated postmastectomy chest wall recurrence Cancer Haffty BG, Hauser A, Choi DH, Parisot N, Rimm DL, King BL, Carter D 2004; 100: 252-256
  • A comparison of five immunlohistochernical biomarkers and HER-2/neu gene amplification by fluorescence in situ hybridization in white and Korean patients with early-onset breast carcinoma CANCER Choi, D. H., Shin, D. B., Lee, M. H., Lee, D. W., Dhandapani, D., Carter, D., King, B. L., Haffty, B. G. 2003; 98 (8): 1587-1595


    The objective of this article was to compare five tumor markers between white women in the U.S. and native Korean women with early-onset breast carcinoma.Sixty Korean women who were diagnosed with breast carcinoma at age 45 years or younger and 60 white women with breast carcinoma who were matched by age were selected for this study. The median age of both groups was 37 years. Paraffin embedded blocks of the primary tumor were processed for immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), p53, cyclin D1, and HER-2/neu.The proportion of tumors that stained positive for ER, PR, p53, and cyclin D1 in the Korean women were 47.5%, 42.4%, 28.8%, and 40.9%, respectively; in the white women, the proportions were 43.9%, 52.6%, 21.1%, and 59.1%, respectively. The differences between the white patients and the Korean patients were not statistically significant with respect to any of those variables. A significant difference was found in the expression of HER-2/neu. Specifically, positive HER-2/neu status was observed in 47.5% of Korean women, compared with overexpression in only 15.8% of white women (P < 0.001). Fluorescence in situ hybridization analysis for HER-2/neu gene amplification on all HER-2/neu positive samples that scored 2 + and 3 + demonstrated a significant difference (P = 0.007) in gene amplification between the two populations. Differences in HER-2/neu positivity were observed for the entire cohort as well as among the subsets of patients with negative and positive lymph node status. No association was found between immunoreactivity for the five markers and axillary lymph node metastasis.The findings of high positivity of HER-2/neu expression and gene amplification in Korean women with early-onset breast carcinoma may have potential implications for local and systemic management of breast carcinoma, especially anti-HER-2/neu therapy for patients with hormone receptor negativity. Further research will be needed to identify biologic and genetic factors and their effects on the survival between different racial groups.

    View details for DOI 10.1002/cncr.11703

    View details for Web of Science ID 000185809800006

    View details for PubMedID 14534873

  • Detection of chromosomal instability in paired breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization CLINICAL CANCER RESEARCH King, B. L., Tsai, S. C., Gryga, M. E., D'Aquila, T. G., Seelig, S. A., Morrison, L. E., Jacobson, K. K., Legator, M. S., WARD, D. C., Rimm, D. L., Phillips, R. F. 2003; 9 (4): 1509-1516


    Ductal lavage is a new modality for collecting exfoliated breast cells with the goal of detecting early neoplasia. The purpose of our study was to evaluate the correlation between cancer-associated abnormalities in breast lesions and exfoliated breast cells collected by ductal lavage.We performed histopathologic, cytologic, and molecular cytogenetic analyses on 39 paired cases of surgically excised breast lesions and ductal lavage specimens collected immediately before surgery.Abnormal cytology was detected in 7 of 15 (47%) of the evaluable lavages collected from malignant cases, versus 4 of 19 (21%) of the evaluable lavages harvested from benign cases for a sensitivity and specificity of 47 and 79%, respectively. Interphase fluorescence in situ hybridization analysis of all evaluable lavages revealed numeric changes on chromosomes 1, 8, 11, and/or 17 in 10 of 14 (71%) specimens from malignant cases versus 2 of 18 (11%) from benign cases for a sensitivity and specificity of 71 and 89%, respectively.Our study demonstrates that cytologic and genetic abnormalities associated with breast cancer progression can be detected in ductal lavage cells collected from women with in situ and invasive breast cancer and suggests that fluorescence in situ hybridization may have superior sensitivity and specificity compared with conventional cytology.

    View details for Web of Science ID 000182067400042

    View details for PubMedID 12684427

  • Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome CANCER RESEARCH Camp, R. L., Dolled-Filhart, M., King, B. L., Rimm, D. L. 2003; 63 (7): 1445-1448


    Using a tissue microarray cohort of 300 breast cancers and 84 samples of normal breast epithelium, we analyzed HER2/neu expression and compared traditional clinical (manual) scoring with a recently developed system for the quantitative measurement of immunohistochemical stains (AQUA). As expected, both methods identified a population (10-15%) of high-HER2-expressing tumors with poor 30-year disease-related survival. Using AQUA analysis, we found that normal epithelium expresses a low but detectable level of HER2 and that 17.5% of tumors exhibit similar low-level HER2 expression. This low group was not definable by manual scoring. Surprisingly, HER2-normal tumors were as aggressive as HER2-overexpressing tumors. Our studies suggest that in situ quantitative measurement of HER2 stratifies breast tumors into three expression levels: normal, intermediate, and high, where both normal and high levels are associated with a worse outcome.

    View details for Web of Science ID 000181896900002

    View details for PubMedID 12670887

  • Immunocytochemical analysis of breast cells obtained by ductal lavage CANCER CYTOPATHOLOGY King, B. L., Crisi, G. M., Tsai, S. C., Haffty, B. G., Phillips, R. F., Rimm, D. L. 2002; 96 (4): 244-249


    Intraductal breast fluids containing exfoliated mammary epithelial cells can be harvested from the breast by ductal lavage to screen for disease-associated cytologic abnormalities. In addition to epithelial cells, breast fluids contain large numbers of mammary foam cells, and the tissue of origin of these foam cells has been the subject of controversy for many years. Immunocytochemical, morphologic, and molecular studies variously have supported a mammary epithelial origin versus a histiocytic origin for this cell type. In the current study, the authors performed immunocytochemical analysis with epithelial specific and macrophage specific antibodies to characterize and quantify breast cells obtained by ductal lavage.Breast fluids were harvested from 19 individual breast ducts in 15 female patients by ductal lavage. Cells from each specimen were processed for immunocytochemical staining using the AE1/AE3 multicytokeratin and CD68 (clone KP1) monoclonal antibodies. Cells were classified as mammary epithelial cells or mammary foam cells on the basis of morphologic criteria, and the cells were counted and evaluated for immunoreactivity with epithelial specific and macrophage specific antibodies.The CD68 macrophage specific antibody stained all ductal lavage cells that exhibited foam cell morphology. The AE1/AE3 multicytokeratin antibody demonstrated strong, positive staining of cells that exhibited epithelial morphology but failed to demonstrate significant staining of mammary foam cells. The lavage specimens contained a range of 3040-278,850 epithelial cells and 2230-90,480 foam cells. The median numbers of epithelial cells and foam cells per lavage sample were 15,680 and 29,200, respectively. The ratio of epithelial cells to foam cells varied among specimens ranging from 3.4 to 0.09 (median, 0.8). Seven of 19 lavage specimens contained more epithelial cells than foam cells, whereas 12 samples contained a greater proportion of foam cells.Immunocytochemical analysis using the AE1/AE3 multicytokeratin and CD68 antibodies supports a histiocytic origin for the majority of mammary foam cells harvested from the ductal system of the human breast by ductal lavage. Although mammary foam cells constitute a significant proportion of the cellular population obtained by ductal lavage, thousands of epithelial cells also are harvested.

    View details for DOI 10.1002/cncr.10719

    View details for Web of Science ID 000177482000008

    View details for PubMedID 12209667

  • The promise and pitfalls of breast fluid proteins as markers for cancer detection CANCER JOURNAL King, B. L. 2002; 8 (4): 295-297

    View details for Web of Science ID 000177383800002

    View details for PubMedID 12184405

  • Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma CLINICAL CANCER RESEARCH Khan, A. J., King, B. L., Smith, B. D., Smith, G. L., DiGiovanna, M. P., Carter, D., Haffty, B. G. 2002; 8 (2): 540-548


    The role of HER-2/neu in squamous cell carcinoma (SCC) of the head and neck is not well defined. The purpose of the current study is to measure the frequency of HER-2/neu expression, to demonstrate HER-2/neu gene amplification in the cases found to be positive for protein overexpression, and to investigate the prognostic significance of overexpression and/or amplification in SCC of the head and neck.A cohort of 77 patients with SCC of the oral cavity or oropharynx, with stage III or IV disease and uniformly treated with surgical resection and postoperative radiation, served as the primary patient population for the study. Of these, 56 patients had adequate follow-up and paraffin-embedded specimens available for analysis. Median follow-up was 6.1 years. Each of the paraffin-embedded specimens were immunohistochemically stained for HER-2/neu expression and graded for intensity of staining by a pathologist. All cases that demonstrated positive staining by immunohistochemistry were analyzed by fluorescence in situ hybridization (FISH) to assess HER-2/neu amplification status.Five-year survival for the 56 evaluable patients was 40%, with 25% experiencing local relapse, 18% regional relapse, and 25% distant relapse. The percentage of tumors staining positive for HER-2/neu by immunohistochemistry was 17%. There was no statistically significant correlation between HER-2/neu and T stage, N stage, tumor grade, survival, or disease-free survival. HER-2/neu expression did correlate with vascular endothelial growth factor expression. FISH analysis revealed four cases that were amplified for HER-2/neu. Of note, of the 4 amplified cases, 2 suffered regional relapse, 1 suffered distant metastasis, and all 4 expired by 5 years of follow-up.This is the first demonstration of HER-2/neu gene amplification by FISH in SCC of the head and neck. FISH validates a previously contested controversial role for HER-2/neu gene overexpression in SCC of the head and neck. The prognostic significance and clinical implications of HER-2/neu expression and amplification in head and neck cancer will require additional studies.

    View details for Web of Science ID 000173908600031

    View details for PubMedID 11839675

  • Ductal lavage and the clinical management of women at high risk for breast carcinoma - A commentary CANCER O'Shaughnessy, J. A., Ljung, B. M., Dooley, W. C., Chang, J., Kuerer, H. M., Hung, D. T., Grant, M. D., Khan, S. A., Phillips, R. F., Duvall, K., Euhus, D. M., King, B. L., Anderson, B. O., Troyan, S. L., Kim, J., Veronesi, U., Cazzaniga, M. 2002; 94 (2): 292-298

    View details for Web of Science ID 000173303800002

    View details for PubMedID 11900214

  • Ductal lavage for detection of cellular atypia in women at high risk for breast cancer JOURNAL OF THE NATIONAL CANCER INSTITUTE Dooley, W. C., Ljung, B. M., Veronesi, U., Cazzaniga, M., Elledge, R. M., O'Shaughnessy, J. A., Kuerer, H. M., Hung, D. T., Khan, S. A., Phillips, R. F., Ganz, P. A., Euhus, D. M., Esserman, L. J., Haffty, B. G., King, B. L., Kelley, M. C., ANDERSON, M. M., Schmit, P. J., Clark, R. R., Kass, F. C., Anderson, B. O., Troyan, S. L., Arias, R. D., Quiring, J. N., Love, S. M., Page, D. L., King, E. B. 2001; 93 (21): 1624-1632


    Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells.Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided.The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported.Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

    View details for Web of Science ID 000171994500010

    View details for PubMedID 11698566

  • Long CAG/CTG repeats in mice MAMMALIAN GENOME King, B. L., Sirugo, G., Nadeau, J. H., Hudson, T. J., Kidd, K. K., Kacinski, B. M., Schalling, M. 1998; 9 (5): 392-393

    View details for Web of Science ID 000073321200012

    View details for PubMedID 9545500

  • Hereditary cancer in men: prostate and testicular cancer Inherited Susceptibility to Cancer: Clinical, Predictive & Ethical Perspectives. Foulkes Narod, S., King, B. L., Hogg, D. edited by Foulkes, W. D., Hodgson, S. V. Cambridge University Press, New York. 1998
  • Repeat expansion detection analysis of (CAG)(n) tracts in tumor cell lines, testicular tumors, and testicular cancer families CANCER RESEARCH King, B. L., Peng, H. Q., Goss, P., Huan, S., Bronson, D., Kacinski, B. M., Hogg, D. 1997; 57 (2): 209-214


    The mutational expansion of triplet repeat microsatellite sequences underlies the transmission of a number of heritable neurological disorders. However, this form of microsatellite instability has not previously been observed in association with malignant disease. Because trinucleotide expansions can dramatically alter gene expression and protein function, we hypothesized that they might occur in neoplastic cells as a mechanism through which to alter cancer genes. Accordingly, we used the repeat expansion detection technique to determine whether (CAG)n triplet repeat expansions were present in DNA from malignant cells. No expansions were observed in a survey of 20 tumor cell lines derived from neoplasms of the breast, ovary, cervix, endometrium, lung, colon, placenta, or hematopoietic system. However, we did observe expanded (CAG)n tracts in DNA from 5 of 11 testicular tumor cell lines and in 1 of 11 sporadic testicular tumors. Examination of the corresponding normal DNA, when available, revealed that some of the expansions were germline in nature. To assess the possibility that (CAG)n expansions underlie some cases of inherited testicular cancer, we also analyzed germline DNA from members of five kindreds predisposed to this malignancy. An increase in (CAG)n tract size was observed in all five families and was particularly striking in one large pedigree in which expansions were observed in three of four affected siblings. These observations raise the possibility that the germline transmission of expanded (CAG)n tracts may play a role in testicular tumorigenesis.

    View details for Web of Science ID A1997WC72100006

    View details for PubMedID 9000556

  • MICROSATELLITE INSTABILITY IN OVARIAN NEOPLASMS BRITISH JOURNAL OF CANCER King, B. L., Carcangiu, M. L., Carter, D., Kiechle, M., Pfisterer, J., Kacinski, B. M. 1995; 72 (2): 376-382


    Microsatellite instability has been observed in a variety of sporadic malignancies, but its existence in sporadic ovarian cancer has been the subject of conflicting reports. We have performed a polymerase chain reaction-based microsatellite analysis of DNAs extracted from the neoplastic and non-neoplastic tissues of 41 ovarian cancer patients. Tumour-associated alterations were observed in seven (17%) of these cases. Clinicopathological correlations revealed that: (1) alterations among tumours classified as serous adenocarcinomas occurred with relatively low frequency (2/24 or 8%); (2) most of the tumours with microsatellite alterations (5/7 or 71%) were of less common histopathological types (epithelial subtypes such as endometrioid and mixed serous and mucinous, or non-epithelial types such as malignant mixed Müllerian or germ cell tumours); (3) tumour-associated alterations were observed in 3/4 (75%) of the patients with stage I tumours vs 4/37 (11%) of the patients with stage II, III and IV tumours (P = 0.01); (4) tumour-associated microsatellite instability was found to occur with similar frequencies among patients with and without clinical features suggestive of familial disease, including positive family history, early onset, or multiple primary tumours. In summary, we have observed microsatellite alterations in the neoplastic tissues of ovarian cancer patients with diverse genetic backgrounds and clinicopathological features. The pattern of alterations is consistent with the possibility that multiple mechanisms may be responsible for microsatellite instability in ovarian neoplasms.

    View details for Web of Science ID A1995RM11600019

    View details for PubMedID 7640221



    In this report we describe the application of a polymerase chain reaction (PCR)-based DNA typing assay to the analysis of tumor cell line identity. We have applied the technique to analyze four tumor cell lines purchased from the American Type Culture Collection (SK-OV-3, SK-BR-3, OVCAR, HeLa) and four lines isolated from the ascites fluids of ovarian cancer patients (YAOVBIX1, YAOVBIX3, OC194, and OC346). In this assay, three polymorphic tetranucleotide microsatellite loci (GABARB1, TH01, and HPRTB) were amplified from tumor cell line DNAs in radioactive PCR-reactions. The products were resolved in polyacrylamide gels and exposed to film to produce individual-specific patterns for five of the cell lines (HeLa, SK-BR-3, OVCAR, YAOVBIX3, and OC194). However, three of the cell lines, SK-OV-3, YAOVBIX1, and OC436 had identical "fingerprints" at all three loci. The probability that the observed profile match could occur between three randomly selected heterologous cell lines was calculated to be 1.32 x 10(-13). On the basis of this analysis, we have identified two independent cross-contamination events involving the SK-OV-3 ovarian adenocarcinoma cell line. The PCR-based analysis of tetranucleotide microsatellite loci is technically straightforward and produces discrete allelic bands associated with known population frequencies, allowing for the unequivocal interpretation of typing patterns.

    View details for Web of Science ID A1994NA16900009

    View details for PubMedID 8129034



    In situ hybridization (ISH) analysis of 24 benign, borderline, and malignant ovarian tumor specimens revealed NEU transcript expression by epithelial elements in approximately two-thirds of the samples and high-level expression in 3 grade 3 adenocarcinomas. Immunohistochemical staining (IHC) of a total of 86 specimens (including 17 of those studied by ISH) localized NEU antigen expression to epithelial cells in 36 of 86 samples with strong membrane staining observed in 12, including 1 benign, 1 borderline serous carcinoma, 3 clear cell/endometrioid carcinomas, and 7 predominantly papillary serous carcinomas with areas of clear cell/endometrioid histology. Clinical correlation of the IHC results for the 72 Stage I-IV invasively malignant neoplasms revealed no statistically significant association of the intensity of NEU IHC staining with either relapse-free or overall survival. However, more of the patients whose tumors showed strong membrane staining for NEU antigen suffered relapses of disease by 3 and 4 years than did patients whose tumors showed weak or no membrane staining. These results suggest a role for the NEU gene product in the physiology of benign ovarian surface epithelium and the neoplastic epithelium of preinvasive borderline and some invasively malignant adenocarcinomas.

    View details for Web of Science ID A1992HK17900009

    View details for PubMedID 1347282



    In this communication, the authors summarize their characterization of eight ovarian adenocarcinoma-derived cell lines for level of neu gene amplification, expression of neu transcripts and protein, and intraperitoneal tumorigenicity in nude mice. Two of the eight cell lines in our study (SKOV3 and YAOVBIX1) exhibited five- to ninefold neu DNA sequence amplification, accompanied by up to 200-fold overexpression of transcripts and protein (p185). Both of these cell lines expressed a major approximately 7.5 kb neu-complementary transcript not previously reported in other neu-positive tumor cell lines. One pair of cell lines (YAOVBIX1 and YAOVBIX3), isolated from a single ovarian carcinoma patient's ascites sample differed dramatically in regard to level of neu gene amplification and expression. Immunohistochemical staining of the primary ovarian tumor from which these two lines were derived demonstrated populations of both neu-positive and neu-negative malignant epithelial cells. Seven of the eight ovarian carcinoma lines produced intra-abdominal tumors after intraperitoneal injection into nude mice, irrespective of level of neu gene expression. This study demonstrates tumor cell heterogeneity with regard to neu gene amplification and expression in an ovarian adenocarcinoma, reveals the overexpression of novel neu-complementary transcripts in two independently isolated ovarian adenocarcinoma cell lines, and suggests that neu gene expression is not required for intraperitoneal tumorigenicity of ovarian carcinoma xenografts in a nude mouse model system.

    View details for Web of Science ID A1992GZ63600005

    View details for PubMedID 1346236

  • FMS (CSF-1 RECEPTOR) AND CSF-1 TRANSCRIPTS AND PROTEIN ARE EXPRESSED BY HUMAN BREAST CARCINOMAS INVIVO AND INVITRO ONCOGENE Kacinski, B. M., Scata, K. A., Carter, D., Yee, L. D., Sapi, E., King, B. L., Chambers, S. K., Jones, M. A., PIRRO, M. H., Stanley, E. R., Rohrschneider, L. R. 1991; 6 (6): 941-952


    The expression in vivo of FMS transcripts and antigen by neoplastic epithelial cells was demonstrated immunohistochemically or by in situ hybridization in sixteen of seventeen human breast carcinoma specimens and one case of sclerosing adenosis. Expression of CSF-1 receptor (FMS) transcripts and protein was also observed in vitro in two or three breast carcinoma-derived cell lines and was dramatically increased by dexamethasone, a potent glucocorticoid and inducer of mammary epithelial cell differentiation. Immunohistochemical staining with an anti-CSF-1 antibody identified neoplastic epithelial cell co-expression of fms and CSF-1 antigens in more than one-third of the fms-positive invasive carcinoma specimens. These results suggest that autocrine and paracrine interactions of the lymphohematopoietic cytokine CSF-1 and its receptor may participate in the biology of human mammary neoplasms.

    View details for Web of Science ID A1991GU62200008

    View details for PubMedID 1829808