E-cadherin expression in primary carcinomas of the breast and its distant metastases

Breast Cancer Research - Tập 5 - Trang 1-6 - 2003
Paul J Kowalski1, Mark A Rubin2, Celina G Kleer1,3
1Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, USA
2Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
3Department of Pathology, 2G332 University Hospital, Ann Arbor, USA

Tóm tắt

Aberrant expression of E-cadherin has been associated with the development of metastases in patients with breast cancer. Even though the expression of E-cadherin has been studied in primary breast tumors, little is known about its expression at the distant metastatic sites. We investigate the relationship between E-cadherin expression in primary breast carcinoma and their distant, non-nodal metastases. Immunohistochemical analysis of E-cadherin was performed in tissues from 30 patients with primary invasive breast carcinoma and their distant metastases. E-cadherin expression was evaluated as normal or aberrant (decreased when compared with normal internal positive controls, or absent). Twenty-two (73%) invasive carcinomas were ductal, and eight (27%) were lobular. Of the primary invasive ductal carcinomas, 55% (12/22) had normal E-cadherin expression and 45% (10/22) had aberrant expression. All of the metastases expressed E-cadherin with the same intensity as (12 tumors) or with stronger intensity than (10 tumors) the corresponding primaries. Of the invasive lobular carcinomas, one of eight (12%) primary carcinomas and none of the metastases expressed E-cadherin in the cell membranes, but they accumulated the protein in the cytoplasm. Aberrant E-cadherin expression is frequent in invasive ductal carcinomas that progress to develop distant metastases. Distant metastases consistently express E-cadherin, often more strongly than the primary tumor. Invasive lobular carcinomas have a different pattern of E-cadherin expression, suggesting a different role for E-cadherin in this form of breast carcinoma.

Tài liệu tham khảo

Haybittle JL, Blamey RW, Elston CW, Johnson J, Doyle PJ, Campbell FC, Nicholson RI, Griffiths K: A prognostic index in primary breast cancer. Br J Cancer. 1982, 45: 361-366. Rosen PR, Groshen S, Saigo PE, Kinne DW, Hellman S: A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol. 1989, 7: 355-366. Danforth DN, Lichter A, Lippman ME: The diagnosis of breast cancer. In Diagnosis and Management of Breast Cancer. Edited by: Danforth Jr DN, Lichter A, Lippman ME. 1988, Philadelphia, PA: WB Saunders, 50-94. Gumbiner BM: Regulation of cadherin adhesive activity. J Cell Biol. 2000, 148: 399-404. 10.1083/jcb.148.3.399. Deman JJ, Van Larebeke NA, Bruyneel EA, Bracke ME, Vermeulen SJ, Vennekens KM, Mareel MM: Removal of sialic acid from the surface of human MCF-7 mammary cancer cells abolishes E-cadherin-dependent cell–cell adhesion in an aggregation assay. In Vitro Cell Dev Biol Anim. 1995, 31: 633-639. Shore EM, Nelson WJ: Biosynthesis of the cell adhesion molecule uvomorulin (E-cadherin) in Madin-Darby canine kidney epithelial cells. J Biol Chem. 1991, 266: 19672-19680. Day ML, Zhao X, Vallorosi CJ, Putzi M, Powell CT, Lin C, Day KC: E-cadherin mediates aggregation-dependent survival of prostate and mammary epithelial cells through the retinoblastoma cell cycle control pathway. J Biol Chem. 1999, 274: 9656-9664. 10.1074/jbc.274.14.9656. Peifer M: Beta-catenin as oncogene: the smoking gun. Science. 1997, 275: 1752-1753. 10.1126/science.275.5307.1752. Gamallo C, Palacios J, Suarez A, Pizarro A, Navarro P, Quintanilla M, Cano A: Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993, 142: 987-993. Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Lochner D, Birchmeier W: E-cadherin-mediated cell–cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991, 113: 173-185. Pierceall WE, Woodard AS, Morrow JS, Rimm D, Fearon ER: Frequent alterations in E-cadherin and alpha- and beta-catenin expression in human breast cancer cell lines. Oncogene. 1995, 11: 1319-1326. Chen WC, Obrink B: Cell–cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells. J Cell Biol. 1991, 114: 319-327. Shimoyama Y, Hirohashi S, Hirano S, Noguchi M, Shimosato Y, Takeichi M, Abe O: Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989, 49: 2128-2133. Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, Debruyne FM, Schalken JA: Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994, 54: 3929-3933. Umbas R, Isaacs WB, Bringuier PP, Xue Y, Debruyne FM, Schalken JA: Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer. Int J Cancer. 1997, 74: 374-377. 10.1002/(SICI)1097-0215(19970822)74:4<374::AID-IJC2>3.0.CO;2-S. Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I: E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993, 53: 1690-1695. Dorudi S, Hanby AM, Poulsom R, Northover J, Hart IR: Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. Br J Cancer. 1995, 71: 614-616. Rasbridge SA, Gillett CE, Sampson SA, Walsh FS, Millis RR: Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol. 1993, 169: 245-250. Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M: Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993, 53: 1696-1701. Palacios J, Benito N, Pizarro A, Suarez A, Espada J, Cano A, Gamallo C: Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. Am J Pathol. 1995, 146: 605-612. Bukholm IK, Nesland JM, Borresen-Dale AL: Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients [see comments]. J Pathol. 2000, 190: 15-19. 10.1002/(SICI)1096-9896(200001)190:1<15::AID-PATH489>3.3.CO;2-C. Bukholm IK, Nesland JM, Karesen R, Jacobsen U, Borresen-Dale AL: E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998, 185: 262-266. 10.1002/(SICI)1096-9896(199807)185:3<262::AID-PATH97>3.0.CO;2-Y. Jones JL, Royall JE, Walker RA: E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma. Br J Cancer. 1996, 74: 1237-1241. Moll R, Mitze M, Frixen UH, Birchmeier W: Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993, 143: 1731-1742. Rosen PP, Oberman HA: Tumors of the Mammary Gland. Atlas of Tumor Pathology. 1993, Washington, DC: Armed Forces Institute of Pathology Tavassoli F: General considerations in breast pathology. In Breast Pathology. Edited by: Tavassoli F. 1999, Connecticut: Appelton & Lange, 27-74. Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991, 19: 403-410. Kleer CG, van Golen KL, Braun T, Merajver SD: Persistent E-cadherin expression in inflammatory breast cancer. Mod Pathol. 2001, 14: 458-464. Rubin MA, Mucci NR, Figurski J, Fecko A, Pienta KJ, Day ML: E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. Hum Pathol. 2001, 32: 690-697. 10.1053/hupa.2001.25902. Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME, Moasser M, Sklarin N, Dickler M, D'Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L, Hudis CA: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001, 19: 2587-2595. Rashid MG, Sanda MG, Vallorosi CJ, Rios-Doria J, Rubin MA, Day ML: Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate. Cancer Res. 2001, 61: 489-492. Nass SJ, Herman JG, Gabrielson E, Iversen PW, Parl FF, Davidson NE, Graff JR: Aberrant methylation of the estrogen receptor and E-cadherin 5' CpG islands increases with malignant progression in human breast cancer. Cancer Res. 2000, 60: 4346-4348. De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, Van Roy F, Cornelisse CJ, Cleton-Jansen AM: 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. Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F: E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. Embo J. 1995, 14: 6107-6115. Berx G, Cleton-Jansen AM, Strumane K, de Leeuw WJ, Nollet F, van Roy F, Cornelisse C: 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. Sarrio D, Moreno-Bueno G, Hardisson D, Sanchez-Estevez C, Guo M, Herman JG, Gamallo C, Esteller M, Palacios J: Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int J Cancer. 2003, 106: 208-215. 10.1002/ijc.11197.