Abstract
Aims—To investigate the expression of α, ß, and γ catenins in oropharyngeal and hypopharyngeal squamous cell carcinoma and their relations to each other, as well as to clinical data, tumour differentiation, and prognosis.
Methods—Primary tumours for analysis were obtained from 138 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemistry was used to evaluate the expression of α, ß, and γ catenins. The expression patterns of all catenins were related to clinical data and survival.
Results—The expression patterns of all three catenins were significantly interrelated. Reduced γ catenin expression was significantly associated with poor histological differentiation. No association was found between α or ß catenin expression and clinicopathological characteristics. In univariate analysis, patients whose tumours had nuclear ß catenin expression had shorter overall survival than patients with no nuclear expression. In Cox multivariate analysis, nuclear ß catenin expression, tumour status (T class), and Karnofsky performance index were independent prognostic factors of overall survival.
Conclusions—Reduced expression of γ catenin is associated with dedifferentiation in primary squamous cell carcinoma of the oropharynx and hypopharynx. The fact that nuclear ß catenin expression independently predicts short overall survival suggests that it might be a valuable prognostic marker in pharyngeal squamous cell carcinoma.
Key Words: catenin • pharyngeal cancer • prognosis
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- Aaltomaa S., Lipponen P., Ala-Opas M., Eskelinen M., Kosma V. M. Alpha-catenin expression has prognostic value in local and locally advanced prostate cancer. Br J Cancer. 1999 May;80(3-4):477–482. doi: 10.1038/sj.bjc.6690381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aberle H., Schwartz H., Kemler R. Cadherin-catenin complex: protein interactions and their implications for cadherin function. J Cell Biochem. 1996 Jun 15;61(4):514–523. doi: 10.1002/(SICI)1097-4644(19960616)61:4%3C514::AID-JCB4%3E3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
- Andrews N. A., Jones A. S., Helliwell T. R., Kinsella A. R. Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer. 1997;75(10):1474–1480. doi: 10.1038/bjc.1997.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anttila M., Kosma V. M., Ji H., Wei-Ling X., Puolakka J., Juhola M., Saarikoski S., Syrjänen K. Clinical significance of alpha-catenin, collagen IV, and Ki-67 expression in epithelial ovarian cancer. J Clin Oncol. 1998 Aug;16(8):2591–2600. doi: 10.1200/JCO.1998.16.8.2591. [DOI] [PubMed] [Google Scholar]
- Back W., Loff S., Jenne D., Bleyl U. Immunolocalization of beta catenin in intestinal polyps of Peutz-Jeghers and juvenile polyposis syndromes. J Clin Pathol. 1999 May;52(5):345–349. doi: 10.1136/jcp.52.5.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bagutti C., Speight P. M., Watt F. M. Comparison of integrin, cadherin, and catenin expression in squamous cell carcinomas of the oral cavity. J Pathol. 1998 Sep;186(1):8–16. doi: 10.1002/(SICI)1096-9896(199809)186:1<8::AID-PATH156>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]
- Bailey T., Biddlestone L., Shepherd N., Barr H., Warner P., Jankowski J. Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation. Am J Pathol. 1998 Jan;152(1):135–144. [PMC free article] [PubMed] [Google Scholar]
- Behrens J. Cadherins and catenins: role in signal transduction and tumor progression. Cancer Metastasis Rev. 1999;18(1):15–30. doi: 10.1023/a:1006200102166. [DOI] [PubMed] [Google Scholar]
- Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
- Bowie G. L., Caslin A. W., Roland N. J., Field J. K., Jones A. S., Kinsella A. R. Expression of the cell-cell adhesion molecule E-cadherin in squamous cell carcinoma of the head and neck. Clin Otolaryngol Allied Sci. 1993 Jun;18(3):196–201. doi: 10.1111/j.1365-2273.1993.tb00829.x. [DOI] [PubMed] [Google Scholar]
- Bukholm I. K., Nesland J. M., Kåresen R., Jacobsen U., Børresen-Dale A. L. E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma. J Pathol. 1998 Jul;185(3):262–266. doi: 10.1002/(SICI)1096-9896(199807)185:3<262::AID-PATH97>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
- Cowin P., Burke B. Cytoskeleton-membrane interactions. Curr Opin Cell Biol. 1996 Feb;8(1):56–65. doi: 10.1016/s0955-0674(96)80049-4. [DOI] [PubMed] [Google Scholar]
- Fukuchi T., Sakamoto M., Tsuda H., Maruyama K., Nozawa S., Hirohashi S. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 1998 Aug 15;58(16):3526–3528. [PubMed] [Google Scholar]
- Garcia-Rostan G., Tallini G., Herrero A., D'Aquila T. G., Carcangiu M. L., Rimm D. L. Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. Cancer Res. 1999 Apr 15;59(8):1811–1815. [PubMed] [Google Scholar]
- Hao X., Tomlinson I., Ilyas M., Palazzo J. P., Talbot I. C. Reciprocity between membranous and nuclear expression of beta-catenin in colorectal tumours. Virchows Arch. 1997 Sep;431(3):167–172. doi: 10.1007/s004280050084. [DOI] [PubMed] [Google Scholar]
- Hirvikoski P., Kumpulainen E. J., Virtaniemi J. A., Helin H. J., Rantala I., Johansson R. T., Juhola M., Kosma V. M. Cytoplasmic accumulation of alpha-catenin is associated with aggressive features in laryngeal squamous-cell carcinoma. Int J Cancer. 1998 Oct 23;79(5):546–550. doi: 10.1002/(sici)1097-0215(19981023)79:5<546::aid-ijc18>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Hoschuetzky H., Aberle H., Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994 Dec;127(5):1375–1380. doi: 10.1083/jcb.127.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hugh T. J., Dillon S. A., Taylor B. A., Pignatelli M., Poston G. J., Kinsella A. R. Cadherin-catenin expression in primary colorectal cancer: a survival analysis. Br J Cancer. 1999 Jun;80(7):1046–1051. doi: 10.1038/sj.bjc.6690461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jawhari A., Jordan S., Poole S., Browne P., Pignatelli M., Farthing M. J. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival. Gastroenterology. 1997 Jan;112(1):46–54. doi: 10.1016/s0016-5085(97)70218-x. [DOI] [PubMed] [Google Scholar]
- Kimura Y., Shiozaki H., Doki Y., Yamamoto M., Utsunomiya T., Kawanishi K., Fukuchi N., Inoue M., Tsujinaka T., Monden M. Cytoplasmic beta-catenin in esophageal cancers. Int J Cancer. 1999 Apr 20;84(2):174–178. doi: 10.1002/(sici)1097-0215(19990420)84:2<174::aid-ijc14>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Lo Muzio L., Staibano S., Pannone G., Grieco M., Mignogna M. D., Cerrato A., Testa N. F., De Rosa G. Beta- and gamma-catenin expression in oral squamous cell carcinomas. Anticancer Res. 1999 Sep-Oct;19(5B):3817–3826. [PubMed] [Google Scholar]
- Lou P., Chen W., Sheen T., Ko J., Hsu M., Wu J. Expression of E-cadherin/catenin complex in nasopharyngeal carcinoma: correlation with clinicopathological parameters. Oncol Rep. 1999 Sep-Oct;6(5):1065–1071. doi: 10.3892/or.6.5.1065. [DOI] [PubMed] [Google Scholar]
- Mattijssen V., Peters H. M., Schalkwijk L., Manni J. J., van 't Hof-Grootenboer B., de Mulder P. H., Ruiter D. J. E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer. 1993 Oct 21;55(4):580–585. doi: 10.1002/ijc.2910550411. [DOI] [PubMed] [Google Scholar]
- Miller J. R., Moon R. T. Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 1996 Oct 15;10(20):2527–2539. doi: 10.1101/gad.10.20.2527. [DOI] [PubMed] [Google Scholar]
- Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [PubMed] [Google Scholar]
- Nakanishi Y., Ochiai A., Akimoto S., Kato H., Watanabe H., Tachimori Y., Yamamoto S., Hirohashi S. Expression of E-cadherin, alpha-catenin, beta-catenin and plakoglobin in esophageal carcinomas and its prognostic significance: immunohistochemical analysis of 96 lesions. Oncology. 1997 Mar-Apr;54(2):158–165. doi: 10.1159/000227681. [DOI] [PubMed] [Google Scholar]
- Nhieu J. T., Renard C. A., Wei Y., Cherqui D., Zafrani E. S., Buendia M. A. Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is associated with increased cell proliferation. Am J Pathol. 1999 Sep;155(3):703–710. doi: 10.1016/s0002-9440(10)65168-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pötter E., Bergwitz C., Brabant G. The cadherin-catenin system: implications for growth and differentiation of endocrine tissues. Endocr Rev. 1999 Apr;20(2):207–239. doi: 10.1210/edrv.20.2.0362. [DOI] [PubMed] [Google Scholar]
- Retera J. M., Leers M. P., Sulzer M. A., Theunissen P. H. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study. J Clin Pathol. 1998 Dec;51(12):891–894. doi: 10.1136/jcp.51.12.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rimm D. L., Caca K., Hu G., Harrison F. B., Fearon E. R. Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma. Am J Pathol. 1999 Feb;154(2):325–329. doi: 10.1016/s0002-9440(10)65278-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ropponen K. M., Eskelinen M. J., Lipponen P. K., Alhava E. M., Kosma V. M. Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma. J Clin Pathol. 1999 Jan;52(1):10–16. doi: 10.1136/jcp.52.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schipper J. H., Frixen U. H., Behrens J., Unger A., Jahnke K., Birchmeier W. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991 Dec 1;51(23 Pt 1):6328–6337. [PubMed] [Google Scholar]
- Schipper J. H., Unger A., Jahnke K. E-cadherin as a functional marker of the differentiation and invasiveness of squamous cell carcinoma of the head and neck. Clin Otolaryngol Allied Sci. 1994 Oct;19(5):381–384. doi: 10.1111/j.1365-2273.1994.tb01252.x. [DOI] [PubMed] [Google Scholar]
- Simcha I., Shtutman M., Salomon D., Zhurinsky J., Sadot E., Geiger B., Ben-Ze'ev A. Differential nuclear translocation and transactivation potential of beta-catenin and plakoglobin. J Cell Biol. 1998 Jun 15;141(6):1433–1448. doi: 10.1083/jcb.141.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sormunen R. T., Leong A. S., Väräniemi J. P., Fernando S. S., Eskelinen S. M. Immunolocalization of the fodrin, E-cadherin, and beta-catenin adhesion complex in infiltrating ductal carcinoma of the breast-comparison with an in vitro model. J Pathol. 1999 Mar;187(4):416–423. doi: 10.1002/(SICI)1096-9896(199903)187:4<416::AID-PATH255>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
- Syrigos K. N., Harrington K., Waxman J., Krausz T., Pignatelli M. Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer. J Urol. 1998 Nov;160(5):1889–1893. [PubMed] [Google Scholar]
- Williams H. K., Sanders D. S., Jankowski J. A., Landini G., Brown A. M. Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med. 1998 Aug;27(7):308–317. doi: 10.1111/j.1600-0714.1998.tb01962.x. [DOI] [PubMed] [Google Scholar]
- Zheng Z., Pan J., Chu B., Wong Y. C., Cheung A. L., Tsao S. W. Downregulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. Hum Pathol. 1999 Apr;30(4):458–466. doi: 10.1016/s0046-8177(99)90123-5. [DOI] [PubMed] [Google Scholar]
- de La Coste A., Romagnolo B., Billuart P., Renard C. A., Buendia M. A., Soubrane O., Fabre M., Chelly J., Beldjord C., Kahn A. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8847–8851. doi: 10.1073/pnas.95.15.8847. [DOI] [PMC free article] [PubMed] [Google Scholar]