Schirrous invasive ductal carcinoma of the breast overexpress p53 oncoprotein
Keywords:
Breast neoplasms, p53 oncoprotein, c-erbB-2 oncoprotein, Hormonal receptors, Invasive ductal carcinoma of the breastAbstract
CONTEXT: Breast cancer is the most important neoplasm in adult women, and its worldwide incidence is growing. The tumoral stroma is very important for modulating the growth and invasion of the tumor itself. The relationship between these two components is not completely understood. Schirrous carcinoma is a variant of ductal invasive carcinoma in which the stroma is very desmoplastic, and the importance of this finding still a motive for debate in the literature. OBJECTIVE: To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells. TYPE OF STUDY: Retrospective study. SETTING: Cancer Hospital A C Camargo and Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. SAMPLE: 107 adult women operated because of ductal invasive carcinoma. The cases were separated into 4 groups according to the desmoplastic reaction – less than 15%, between 15-50%, 51-85%, and more than 85% fibrosis. The grade of fibrosis was determined by picrus-sirius staining and quantified by using a microscope with a stereo-imaging grid. Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein. MAIN MEASUREMENTS: Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53. RESULTS: The results showed that schirrous carcinoma expresses oncoprotein p53 more frequently than other carcinomas with less extensive desmoplastic reaction. There were no differences between the grade of fibrosis and the other biological markers. CONCLUSION: The intense stromatous reaction in invasive ductal carcinoma may modulate the expression of p53. Further investigations should be made with the aim of understanding how this expression determines the proliferative activity in schirrous carcinoma, and whether this overexpression is secondary to mutation of the p53 gene or due to modulation of other molecules of the stroma.
Downloads
References
Instituto Nacional do Câncer. Estimativa da incidência e mortalidade por câncer no Brasil; 1997.
Iozzo RV. Tumor stroma as a regulator of neoplastic behavior: agonistic and antagonistic elements embedded in the same con- nective tissue. Lab Invest 1995;73:157-9.
Rosen PP. Biological Markers of prognosis. In: Rosen PP, editor. Breast Pathology. Philadelphia: Lippincott-Raven: 1997.
Hasebe T, Tsuda H, Tsubono Y, Imoto S, Mukai K. Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognos- tic factor parameter for tumor recurrence and tumor death within three years after initial operation. Jpn J Cancer Res 1997;88:590-9.
Hasebe T, Tsuda H, Hirohashi S, et al . Fibrotic focus in infiltrat- ing ductal carcinoma of the breast: a significant histopathological prognostic parameter for predicting the long-term survival of the patients. Breast Cancer Res Treat 1998;49:195-208.
Cardone A, Tolino A, Zarcone R, Borruto G, Tartaglia E. Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer. Panminerva Med 1997;39:147-7.
Greenblatt MS, Bennett WP, Hollstein M, Harris CC. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994;54:4855-78.
Karey KP, Sirbasku DA. Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17beta estradiol. Cancer Res 1988;48:4083-9.
Haslam SZ, Couterman LJ. Mammary stroma modulate hormo- nal responsiveness of mammary epithelium in vivo in the mouse. Endocrinology 1991;29-2017-23.
Bertin N, Clezardin P, Kubiak R, Frappart L. Thrombospondin-1 and 2-Messenger RNA expression in normal, benign, and neoplastic human breast tissue: correlation with prognostic factors, tumor ang- iogenesis, and fibroblastic desmoplasia. Cancer Res 1997;57:396-9
Iochim EE, Athanassiadou SE, Kamina S, Carassavoglu K, Agnantis NJ. Matrix metalloproteinase expression in human breast cancer: an immunohistochemical study including correlation with cathepsin D, type IV collagen, laminin, fibronectin, EGFR, c- erb-B2 oncoprotein, p53, steroid receptor status and proliferative index. Anticancer Res 1998;18:1665-70.
Hojo S, Fujita J, Yamadori I, et al. Heterogeneous point muta- tions of the p53 gene in pulmonary fibrosis. Eur Respir J 1998;12:1404-8.
Ambros RA, Kallakury BV, Malfetano JH, Mihm MC Jr. Cytokine, cell adhesion receptor, and tumor suppressor gene expression in vulvar squamous carcinoma: correlation with prominent fibromyxoid stro- mal response. Int J Gynecol Pathol 1996;15:320-5.
Wagner M, Luhrs H, Kloppel G, Adler G, Schmid RM. Malig- nant transformation of duct-like cells originating from acini in transforming growth factor transgenic mice. Gastroenterology 1998;115:1254-62.
Mezi S, Aloise G, Marzullo A, et al. Prognostic significance of desmoplasia in breast carcinoma. A preliminary clinical study. G Chir 1997;18:263-8.
Horiguchi J, Iino Y, Takei H, Morishita Y. Prognostic significance of c-erbB-2 expression in invasive ductal carcinoma of the breast. Jpn J Clin Oncol 1995;25:119-23.
