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Erschienen in: Breast Cancer Research 1/1999

01.12.1999 | Review

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

verfasst von: Pinchas P Osin, Sunil R Lakhani

Erschienen in: Breast Cancer Research | Ausgabe 1/1999

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Abstract

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D1. Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations.
Literatur
1.
Zurück zum Zitat Breast Cancer Linkage Consortium : Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet. 1997, 349: 1505-1510. 10.1016/S0140-6736(96)10109-4.CrossRef Breast Cancer Linkage Consortium : Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet. 1997, 349: 1505-1510. 10.1016/S0140-6736(96)10109-4.CrossRef
2.
Zurück zum Zitat Lakhani SR, Jacquemier J, Sloane JP, et al: Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998, 90: 1138-1145. 10.1093/jnci/90.15.1138.CrossRefPubMed Lakhani SR, Jacquemier J, Sloane JP, et al: Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998, 90: 1138-1145. 10.1093/jnci/90.15.1138.CrossRefPubMed
3.
Zurück zum Zitat De Leeuw WJ, Berx G, Vos CB, et al: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997, 183: 404-411. 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.CrossRefPubMed De Leeuw WJ, Berx G, Vos CB, et al: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997, 183: 404-411. 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.CrossRefPubMed
4.
Zurück zum Zitat Berx G, Cleton-Jansen AM, Strumane K, et al: E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene . 1996, 13: 1919-1925.PubMed Berx G, Cleton-Jansen AM, Strumane K, et al: E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene . 1996, 13: 1919-1925.PubMed
5.
Zurück zum Zitat Guilford P, Hopkins J, Harraway J, et al: E-cadherin germline mutations in familial gastric cancer. Nature. 1998, 392: 402-405. 10.1038/32918.CrossRefPubMed Guilford P, Hopkins J, Harraway J, et al: E-cadherin germline mutations in familial gastric cancer. Nature. 1998, 392: 402-405. 10.1038/32918.CrossRefPubMed
6.
Zurück zum Zitat Osborne CK: Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat. 1998, 51: 227-238. 10.1023/A:1006132427948.CrossRefPubMed Osborne CK: Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat. 1998, 51: 227-238. 10.1023/A:1006132427948.CrossRefPubMed
7.
Zurück zum Zitat Henderson IC, Patek AJ: The relationship between prognostic and predictive factors in the management of breast cancer. Breast Cancer Res Treat. 1998, 52: 261-288. 10.1023/A:1006141703224.CrossRefPubMed Henderson IC, Patek AJ: The relationship between prognostic and predictive factors in the management of breast cancer. Breast Cancer Res Treat. 1998, 52: 261-288. 10.1023/A:1006141703224.CrossRefPubMed
8.
Zurück zum Zitat Osin P, Gusterson BA, Philp E, et al: Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. Eur J Cancer. 1998, 34: 1683-1686. 10.1016/S0959-8049(98)00248-2.CrossRefPubMed Osin P, Gusterson BA, Philp E, et al: Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. Eur J Cancer. 1998, 34: 1683-1686. 10.1016/S0959-8049(98)00248-2.CrossRefPubMed
9.
Zurück zum Zitat Osin P, Crook T, Powles T, Peto J, Gusterson B: Hormone status of in-situ cancer in BRCA1 and BRCA2 mutation carriers [letter]. Lancet. 1998, 351: 1487-10.1016/S0140-6736(98)24020-7.CrossRefPubMed Osin P, Crook T, Powles T, Peto J, Gusterson B: Hormone status of in-situ cancer in BRCA1 and BRCA2 mutation carriers [letter]. Lancet. 1998, 351: 1487-10.1016/S0140-6736(98)24020-7.CrossRefPubMed
10.
Zurück zum Zitat Johannsson OT, Idvall I, Anderson C, et al: Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer. 1997, 33: 362-371.CrossRefPubMed Johannsson OT, Idvall I, Anderson C, et al: Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer. 1997, 33: 362-371.CrossRefPubMed
11.
Zurück zum Zitat Armes JE, Trute L, White D, et al: Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. Cancer Res. 1999, 59: 2011-2017.PubMed Armes JE, Trute L, White D, et al: Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. Cancer Res. 1999, 59: 2011-2017.PubMed
12.
Zurück zum Zitat Robson M, Rajan P, Rosen PP, et al: BRCA-associated breast cancer: absence of a characteristic immunophenotype. Cancer Res. 1998, 58: 1839-1842.PubMed Robson M, Rajan P, Rosen PP, et al: BRCA-associated breast cancer: absence of a characteristic immunophenotype. Cancer Res. 1998, 58: 1839-1842.PubMed
13.
Zurück zum Zitat Ioakim-Liossi A, Karakitsos P, Markopoulos C, et al: Expression of pS2 protein and estrogen and progesterone receptor status in breast cancer. Acta Cytol. 1997, 41: 713-716.CrossRefPubMed Ioakim-Liossi A, Karakitsos P, Markopoulos C, et al: Expression of pS2 protein and estrogen and progesterone receptor status in breast cancer. Acta Cytol. 1997, 41: 713-716.CrossRefPubMed
14.
Zurück zum Zitat Ross JS, Fletcher JA: HER-2/neu (c-erb-B2) gene and protein in breast cancer. Am J Clin Pathol. 1999, 112(suppl 1): S53-S67. Ross JS, Fletcher JA: HER-2/neu (c-erb-B2) gene and protein in breast cancer. Am J Clin Pathol. 1999, 112(suppl 1): S53-S67.
15.
Zurück zum Zitat Rudolph P, Olsson H, Bonatz G, et al: Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications. J Pathol. 1999, 187: 207-216. 10.1002/(SICI)1096-9896(199901)187:2<207::AID-PATH223>3.3.CO;2-L.CrossRefPubMed Rudolph P, Olsson H, Bonatz G, et al: Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications. J Pathol. 1999, 187: 207-216. 10.1002/(SICI)1096-9896(199901)187:2<207::AID-PATH223>3.3.CO;2-L.CrossRefPubMed
16.
Zurück zum Zitat Elledge RM, Allred DC: Prognostic and predictive value of p53 and p21 in breast cancer. Breast Cancer Res Treat. 1998, 52: 79-98. 10.1023/A:1006163101948.CrossRefPubMed Elledge RM, Allred DC: Prognostic and predictive value of p53 and p21 in breast cancer. Breast Cancer Res Treat. 1998, 52: 79-98. 10.1023/A:1006163101948.CrossRefPubMed
17.
Zurück zum Zitat Crook T, Brooks LA, Crossland S, et al: p53 mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours. Oncogene. 1998, 17: 1681-1689. 10.1038/sj.onc.1202106.CrossRefPubMed Crook T, Brooks LA, Crossland S, et al: p53 mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours. Oncogene. 1998, 17: 1681-1689. 10.1038/sj.onc.1202106.CrossRefPubMed
18.
Zurück zum Zitat Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA: p53 mutations in BRCA1-associated familial breast cancer. Lancet. 1997, 350: 638-639.CrossRefPubMed Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA: p53 mutations in BRCA1-associated familial breast cancer. Lancet. 1997, 350: 638-639.CrossRefPubMed
19.
Zurück zum Zitat Smith PD, Crossland S, Parker G, et al: Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions. Oncogene. 1999, 18: 2451-2459. 10.1038/sj.onc.1202565.CrossRefPubMed Smith PD, Crossland S, Parker G, et al: Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions. Oncogene. 1999, 18: 2451-2459. 10.1038/sj.onc.1202565.CrossRefPubMed
20.
Zurück zum Zitat McClelland RA, Gee JM, O'Sullivan L, et al: p21(WAF1) expression and endocrine response in breast cancer. J Pathol. 1999, 188: 126-132. 10.1002/(SICI)1096-9896(199906)188:2<126::AID-PATH340>3.3.CO;2-F.CrossRefPubMed McClelland RA, Gee JM, O'Sullivan L, et al: p21(WAF1) expression and endocrine response in breast cancer. J Pathol. 1999, 188: 126-132. 10.1002/(SICI)1096-9896(199906)188:2<126::AID-PATH340>3.3.CO;2-F.CrossRefPubMed
21.
Zurück zum Zitat el-Deiry WS, Harper JW, O'Connor PM, et al: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res . 1994, 54: 1169-1174.PubMed el-Deiry WS, Harper JW, O'Connor PM, et al: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res . 1994, 54: 1169-1174.PubMed
22.
Zurück zum Zitat Tan P, Cady B, Wanner M, et al: The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 1997, 57: 1259-1263.PubMed Tan P, Cady B, Wanner M, et al: The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 1997, 57: 1259-1263.PubMed
23.
24.
Zurück zum Zitat Robson M, Gilewski T, Haas B, et al: BRCA-associated breast cancer in young women. J Clin Oncol. 1998, 16: 1642-1649.PubMed Robson M, Gilewski T, Haas B, et al: BRCA-associated breast cancer in young women. J Clin Oncol. 1998, 16: 1642-1649.PubMed
25.
Zurück zum Zitat Gillett CE, Lee AH, Millis RR, Barnes DM: Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia. J Pathol. 1998, 184: 396-400. 10.1002/(SICI)1096-9896(199804)184:4<396::AID-PATH1259>3.3.CO;2-7.CrossRefPubMed Gillett CE, Lee AH, Millis RR, Barnes DM: Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia. J Pathol. 1998, 184: 396-400. 10.1002/(SICI)1096-9896(199804)184:4<396::AID-PATH1259>3.3.CO;2-7.CrossRefPubMed
26.
Zurück zum Zitat McMahon C, Suthiphongchai T, DiRenzo J, Ewen ME: P/CAF associates with cyclin D1 and potentiates its activation of the estrogen receptor. Proc Natl Acad Sci USA. 1999, 96: 5382-5387. 10.1073/pnas.96.10.5382.CrossRefPubMedPubMedCentral McMahon C, Suthiphongchai T, DiRenzo J, Ewen ME: P/CAF associates with cyclin D1 and potentiates its activation of the estrogen receptor. Proc Natl Acad Sci USA. 1999, 96: 5382-5387. 10.1073/pnas.96.10.5382.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Neuman E, Ladha MH, Lin N, et al: Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol. 1997, 17: 5338-5347.CrossRefPubMedPubMedCentral Neuman E, Ladha MH, Lin N, et al: Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol. 1997, 17: 5338-5347.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Barnes DM, Gillett CE: Cyclin D1 in breast cancer. Breast Cancer Res Treat. 1998, 52: 1-15. 10.1023/A:1006103831990.CrossRefPubMed Barnes DM, Gillett CE: Cyclin D1 in breast cancer. Breast Cancer Res Treat. 1998, 52: 1-15. 10.1023/A:1006103831990.CrossRefPubMed
29.
Zurück zum Zitat Duffy MJ: Proteases as prognostic markers in cancer. Clin Cancer Res. 1996, 2: 613-618.PubMed Duffy MJ: Proteases as prognostic markers in cancer. Clin Cancer Res. 1996, 2: 613-618.PubMed
30.
Zurück zum Zitat Rochefort H, Liaudet-Coopman E: Cathepsin D in cancer metastasis: a protease and a ligand. APMIS. 1999, 107: 86-95.CrossRefPubMed Rochefort H, Liaudet-Coopman E: Cathepsin D in cancer metastasis: a protease and a ligand. APMIS. 1999, 107: 86-95.CrossRefPubMed
31.
Zurück zum Zitat Fulco RA, Petix M, Salimbeni V, Torre EA: Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer. Minerva Med. 1998, 89: 5-10.PubMed Fulco RA, Petix M, Salimbeni V, Torre EA: Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer. Minerva Med. 1998, 89: 5-10.PubMed
32.
Zurück zum Zitat Gonzalez-Vela MC, Garijo MF, Fernandez F, Buelta L, Val-Bernal JF: Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma. Histopathology. 1999, 34: 35-42. 10.1046/j.1365-2559.1999.00548.x.CrossRefPubMed Gonzalez-Vela MC, Garijo MF, Fernandez F, Buelta L, Val-Bernal JF: Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma. Histopathology. 1999, 34: 35-42. 10.1046/j.1365-2559.1999.00548.x.CrossRefPubMed
Metadaten
Titel
The pathology of familial breast cancer: Immunohistochemistry and molecular analysis
verfasst von
Pinchas P Osin
Sunil R Lakhani
Publikationsdatum
01.12.1999
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 1/1999
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr11

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