Her-2/neu overexpression and amplification in uterine papillary serous carcinoma

Brian Slomovitz, Russell R. Broaddus, Thomas W. Burke, Nour Sneige, Pamela T. Soliman, Weiguo Wu, Charlotte C. Sun, Mark F. Munsell, David M. Gershenson, Karen H. Lu

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Abstract

Purpose: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. Patients and Methods: Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. Results: Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P ≤ .05). Conclusion: Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.

Original languageEnglish (US)
Pages (from-to)3126-3132
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number15
DOIs
StatePublished - 2004
Externally publishedYes

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Papillary Carcinoma
Gene Amplification
Immunohistochemistry
Neoplasms
erbB-2 Genes
San Francisco
Endometrial Neoplasms
Fluorescence In Situ Hybridization
Proportional Hazards Models
Medical Records
Carcinogenesis
Lymph Nodes
Clinical Trials
Staining and Labeling
Neoplasm Metastasis
Membranes
Survival
Mortality
Proteins
Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Slomovitz, B., Broaddus, R. R., Burke, T. W., Sneige, N., Soliman, P. T., Wu, W., ... Lu, K. H. (2004). Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. Journal of Clinical Oncology, 22(15), 3126-3132. https://doi.org/10.1200/JCO.2004.11.154

Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. / Slomovitz, Brian; Broaddus, Russell R.; Burke, Thomas W.; Sneige, Nour; Soliman, Pamela T.; Wu, Weiguo; Sun, Charlotte C.; Munsell, Mark F.; Gershenson, David M.; Lu, Karen H.

In: Journal of Clinical Oncology, Vol. 22, No. 15, 2004, p. 3126-3132.

Research output: Contribution to journalArticle

Slomovitz, B, Broaddus, RR, Burke, TW, Sneige, N, Soliman, PT, Wu, W, Sun, CC, Munsell, MF, Gershenson, DM & Lu, KH 2004, 'Her-2/neu overexpression and amplification in uterine papillary serous carcinoma', Journal of Clinical Oncology, vol. 22, no. 15, pp. 3126-3132. https://doi.org/10.1200/JCO.2004.11.154
Slomovitz, Brian ; Broaddus, Russell R. ; Burke, Thomas W. ; Sneige, Nour ; Soliman, Pamela T. ; Wu, Weiguo ; Sun, Charlotte C. ; Munsell, Mark F. ; Gershenson, David M. ; Lu, Karen H. / Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 15. pp. 3126-3132.
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abstract = "Purpose: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. Patients and Methods: Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10{\%} of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. Results: Twelve (18{\%}) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P ≤ .05). Conclusion: Positive IHC overexpression of Her-2/neu was seen in 18{\%} of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.",
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AU - Slomovitz, Brian

AU - Broaddus, Russell R.

AU - Burke, Thomas W.

AU - Sneige, Nour

AU - Soliman, Pamela T.

AU - Wu, Weiguo

AU - Sun, Charlotte C.

AU - Munsell, Mark F.

AU - Gershenson, David M.

AU - Lu, Karen H.

PY - 2004

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N2 - Purpose: Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. Patients and Methods: Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. Results: Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P ≤ .05). Conclusion: Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.

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