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Abstract

The distribution of transforming growth factor-alpha (TGF-alpha) and c-erbB-2 proteins was immunohistochemically analyzed in 49 epithelial ovarian neoplasms to determine their implication as molecular modulators of epithelial ovarian cancer progression and as possible prognosticators of outcome. TGF-alpha cytoplasmic immunoreactivity was strongly positive in 100% of adenomas (ADs)(N=11) and tumors of low malignant potential (LMPs)(N=17) but in only 19% of invasive carcinomas (ICAs)(N=21). TGF-alpha immunoreactivity was selective of the ovarian epithelium. Interestingly, in the TGF-alpha-positive carcinomas, the monoclonal antibody decorated the better-differentiated areas of the tumor (ie, areas with papillary architecture), leaving the less differentiated solid areas unstained. Strong p185 c-erb B-2 protein cytoplasmic immunoreactivity was present in 45% of ADs but also in 48% of ICAs. The LMPs, however, expressed c-erbB-2 only at low frequency. These data suggest the involvement of c-erbB-2 in the progression of some ovarian carcinomas but not others. Conversely, the strong TGF-alpha expression in ADs and LMPs, which fades in ICAs, implies an alteration of the TGF-alpha expression in the progression of epithelial ovarian tumors. Failure of the poorly differentiated carcinomas to decorate with TGF-alpha seems to indicate that TGF-alpha is a marker of tumor grade. Int J Surg Pnthol4(3):00-00, 1997

Keywords

ovarian epithelial tumors immunohistochemistry transforming growth factor-alpha c-erbB-2.

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References

Wingo PA , Tong T. , Bolden S. Cancer statistics 1995. CA 45:8-30, 1995

Nicosia SV , Nicosia RF Neoplasms of ovarian meothelium. In Azar HA (ed): Pathology of human neoplasms. Raven Press, New York, pp. 435-486, 1988

Serov SF , Scully RE Histological typing of ovarian tumors. In International histological classification of tumors, No. 9. World Health Organization, Geneva, 1973

Russell P. The pathological assessmentofovarian neo-plasma. II. The proliferating "epithelial" tumors. Pathology 11:251-282, 1979

Bell DA , Weinstock MA , Scully RE Peritoneal implants of ovarian serous borderlinetumors. Cancer 62:2212-2222, 1988

Watkin W. , Silvio EG , Gershonson DM Mucinous carcinoma of the ovary. Cancer 69:208-212, 1992

Leake JF , Currie JL , Rosenhein NB , Woodruff JD Long-term follow up of serous ovarian tumors of low malignant potential . Gynecol Oncol 47:150-158,1992

De Nictolis M. , Montironi R. , Tommasoni S. , et al. Serous borderline tumors of the ovary . Cancer 70:152-160, 1992

Nicosia SV , Saunders BO , Acevedo-Duncan M. , et al. Pailiobiology of ovarian mesothelium. In Familiari G , Makabe G , Motta PM (eds): uitrastruaure of the ovary. Kluiver Academic Publishers, Boston , pp. 287-310,1991

10.

Pierro E. , Nicosia SV , Saunders B. , et al. Influence of growth factors on proliferation and morphogenesis of ovarian mesothelial cells in vitro. Biol Reprod 54:660-669, 1996

11.

Haldane JS , Hird V. , Hughes CM , Gullick WJ : c-erbB-2 oncogene expression in ovarian cancer. J Pathol 162:231-237, 1990

12.

Slamon DJ , Godolphin W. , Jones LA , et al. Studies of the HER-2/new protooncogene in human breast and ovarian cancer. Science 244:707-712, 1989

13.

Ito K. , Sasano H. , Ozawa N. , et al. Immunolocalization of epidermal growth factor receptor and c-erbB-2 oncogene product in human ovarian carcinoma. Int J Gynecol Pathol 11:253-257, 1992

14.

Kommoss F. , Wintzer HO , Von Kleist S. , et al. In situ distribution of transforming growth factor α in normal human tissues and in malignant tumors of the ovary. J Pathol 162:223-230, 1990

15.

Tyson FL , Boyer CM , Kaufman R. , et al. Expression and amplification of the ker-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines. Am J Obst Gynecol 165:640-646, 1991

16.

Bast RC , Boyer CM , Jacobs I. , et al. Cell growth regulation in epithelial ovarian cancer. Cancer 71:4597-4601, 1993

17.

Bauknecht T. , Kiechle M. , Bauer G. , Siebers J. Characterization of growth factors in human ovarian carcinomas. Cancer Res 46:2614-2618, 1986

18.

Kohler M. , Janz I. , Winzer HO , et al. The expression of EGF receptors, EGF-like factors and c-myc in ovarian and cervical carcinomas and their potential clinical significance . Anticancer Res 9:1537-1548, 1989

19.

Kommoss F. , Bauknecht T. , Birmelin G. , et al. Oncogene and growth factor expression in ovarian cancer. Acta Obstet Gynecol Scand 155 (suppl 71): 19-24,1992

20.

Berchuck A. , Kohler M. , Bast RC Oncogenes in ovarian cancer. Hematol/Oncol Clin North Am 6:813-826, 1992

21.

Berchuck A. , Kamel A. , Whitaker R. , et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50:4087-4091, 1990

22.

Shi SR , Key ME , Kalza KL Antigen retrieval in formalin-fixed paraffin-embedded tissues. An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741-748, 1991

23.

Stromberg K. , Collins TJ IV , Gordon AW , et al. Transforming frowth factor-α acts as an autocrine growth factor in ovarian carcinoma cell lines. Cancer Res 52:341-347, 1992

24.

Dean C. , Modjtakedi H. , Eccles S. , et al. Immunotherapy with antibodies to the EGF receptor. Int J Cancer (suppl) 8:103-107, 1994

25.

Bauknecht T. , Birmelin G. , Kommoss F. : Clinical significance of oncogenes and growth factors in ovarian carcinomas . Steroid Biochem Mol Biol 37:855-862, 1990

26.

Christen RD , Hom DK , Porter DC , et al. Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. J Clin Invest 8b:1632-1640, 1990

27.

Bauknecht T. , Angel P. , Kohler M. , et al. Gene structure and expression analysis of the epidermal growth factor recept, transforming growth factor alpha, myc, jun, and metallothionein in human ovarian carcinomas. Cancer 71:419-429, 1993

28.

Slamon DJ , Clark GM , Wong SG Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177-182, 1987

29.

Felip E. , Del Campo JM , Rubio D. , et al. Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy. Cancer 75:2147-2152, 1995

30.

Simpson RJ , Phillips HA , Lessells AM , et al. c-erbB-2 growth-factor-receptor proteins in ovarian tumors. Int J Cancer 64:202-206, 1995

31.

Sasano H. , Garrett CT , Wilkinson DS , et al. Protooncogene amplification and tumor ploidy in human ovarian neoplasms. Hum Pathol 21:382-391, 1990

32.

Mileo AM , Fanuel M. , Battaglia F. , et al. Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries. Int J Biol Markers 7:114-118, 1992

33.

Fajac A. , Renard J. , Lhomme C. , et al. c-erbB-2 gene amplification and protein expression in ovarian epithelial tumors: Evaluation of their respective prognostic significance by multivariate analysis. Int J Cancer 64:146-151, 1995

34.

Marth C. , Lang T. , Cronauer MV , et al. Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma cells. Int J Cancer 52:311-316, 1992

Transforming Growth Factor-alpha and c-erbB-2 Oncogene Products in Ovarian Epithelial Tumors

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