Ozan BARUTÇU, Medine KARA, Aslı MURATLI, Oğuz GÜÇLÜ, Sefa DEREKÖY

Açık parsiyel larenjektomi hastalarında Ki-67 c-erbB-2 ve E-kaderin ekspresyonlarının klinik önemi

Amaç: Bu çalışmada gırtlak kanserlerinde klinikopatolojik değişkenler ile ilgili biyo-göstergeler ve servikal lenf nodu invazyonu, nüks, uzak metastaz ve sağkalım riskleri arasındaki ilişkinin analiz edilmesi amaçlandı.Hastalar ve Yöntemler: Larenks kanseri olan 41 hasta retrospektif olarak incelendi. E-kaderin, Ki-67, c-erbB-2 ekspresyonları, tümörün yeri, farklılaşması, servikal lenf nodu metastazı, perinöral, perivasküler, perikapsüler invazyon riski ile nüks ve sağkalım süresi arasındaki ilişki istatistiksel olarak değerlendirildi.Bulgular: T-evresi ile sağkalım oranları, perikapsüler invazyonu ve en düşük sağkalım oranları arasında anlamlı ilişki bulundu. E-kaderin, Ki-67, c-erbB-2 ekspresyonları ile tümörün klinikopatolojik değişkenleri arasında anlamlı ilişki bulunmadı. Güçlü E-kaderin boyaması ile Ki-67 proliferasyon indeksi arasında pozitif ilişki saptandı.Sonuç: Bu göstergeler larenks kanseri için güvenilir prognostik ve öngördürücü faktörler değildir. E-kaderin ekspresyonu, hücre-hücre adezyonlarını sağlayan farklılaşmış ve daha az invaziv kanserlerde iyi korunup farklılaşmamış kanserlerde azaltılmıştır. E-kaderin ve Ki-67 proliferasyonu arasındaki pozitif ilişki gösteriyor ki larenks kanserlerinin histopatolojik farklılaşması, yüksek proliferasyon indeksine rağmen sürdürülmektedir

Anahtar Kelimeler:

C-erbB-2, klinikopatolojik değişkenler, E-kaderin, Ki-67, larenks kanseri

Clinical significance of Ki-67, c-erbB-2 and E-cadherin expressions in open partial laryngectomy patients

Objectives: This study aims to analyze the correlation between biomarkers and risks of cervical lymph node invasion, recurrence, distant metastasis and survival regarding the clinicopathological variables in laryngeal cancers. Patients and Methods: Forty-one patients with laryngeal cancers were examined retrospectively. The correlations evaluated between E-cadherin, Ki-67, c-erbB-2 expressions, tumor site, differentiation, the risk of cervical lymph node metastasis, perineural, perivascular, pericapsular invasion and recurrence as well as survival time. Results: There was significant correlation between T-grade and the survival rates, and between pericapsular invasion and the lowest survival rates. There was no significant correlation between E-cadherin, Ki-67, c-erbB-2 expressions and clinicopathological variables of tumor. Positive correlation between strong stain of E-cadherin and Ki-67 proliferation index was determined. Conclusion: These markers are not reliable prognostic and predictive factors for laryngeal cancers. E-cadherin expression was protected in well-differentiated and less invasive cancers, which maintain their cell-cell adhesions whereas it was reduced in undifferentiated cancers. Positive correlation between E-cadherin and Ki-67 proliferation shows that histopathological differentiation of laryngeal cancers is maintained in spite of the high proliferation index.

Keywords:

C-erbB-2, clinicopathological variables, E-cadherin, Ki-67, Larynx cancer,

PDF

___

Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med 2001;345:1890-900.
Galera-Ruiz, H, Ríos-Moreno MJ, González-Cámpora R, Ortega I, Fernández A, García-Escudero A, et al. The cadherin-catenin complex in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2012;269:1183-8.
Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, et al. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 1991;113:173-85.
Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000;19:3159-67.
Shah NG, Trivedi TI, Tankshali RA, Goswami JV, Jetly DH, Shukla SN, et al. Prognostic significance of molecular markers in oral squamous cell carcinoma: amultivariate analysis. Head Neck 2009;31:1544-56.
de Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, Cordeiro RC, Bacchi CE. Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma. Am J Clin Pathol 2006;126:284-93.
Rodrigo JP, Dominguez F, Suárez V, Canel M, Secades P, Chiara MD. Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007;133:145-50.
Mittari E, Charalabopoulos A, Batistatou A, Charalabopoulos K. The role of E-cadherin/catenin complex in laryngeal cancer. Exp Oncol 2005;27:257-61.
Takes RP, Baatenburg de Jong RJ, Schuuring E, Hermans J, Vis AA, Litvinov SV, et al. Markers for assessment of nodal metastasis in laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 1997;123:412-9.
Li JJ, Zhang GH, Yang XM, Li SS, Liu X, Yang QT, et al. Reduced E-cadherin expression is associated with lymph node metastases in laryngeal squamous cell carcinoma. Auris Nasus Larynx 2012;39:186-92.
Liu M, Lawson G, Delos M, Jamart J, Chatelain B, Remacle M, et al. Prognostic value of cell proliferation markers, tumour suppressor proteins and cell adhesion molecules in primary squamous cell carcinoma of the larynx and hypopharynx. Eur Arch Otorhinolaryngol 2003;260:28-34.
Rodrigo JP, Domínguez F, Alvarez C, Manrique C, Herrero A, Suárez C. Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features. Eur J Cancer 2002;38:1059-64.
Kurtz KA, Hoffman HT, Zimmerman MB, Robinson RA. Decreased E-cadherin but not beta-catenin expression is associated with vascular invasion and decreased survival in head and neck squamous carcinomas. Otolaryngol Head Neck Surg 2006;134:142-6.
Gutiérrez VF, Marcos CÁ, Llorente JL, Guervós MA, Iglesias FD, Tamargo LA, et al. Genetic profile of second primary tumors and recurrences in head and neck squamous cell carcinomas. Head Neck 2012;34:830-9.
Krecicki T, Jeleń M, Zalesska-Krecicka M. C-erbB-2 immunostaining in laryngeal cancer. Acta Otolaryngol 1999;119:392-5.
Kazkayasi M, Hücümenoğlu S, Siriner GI, Hücümenoğlu M. Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma. Eur Arch Otorhinolaryngol 2001;258:329-35.
Weinstein GS, Nuamah IF, Tucker J, Montone K. Evaluation of HER-2/neu (c-erbB-2) oncogene expression in whole organ sections of supraglottic squamous cell carcinoma. Ann Otol Rhinol Laryngol 1996;105:275-9.
Silva SD, Cunha IW, Younes RN, Soares FA, Kowalski LP, Graner E. ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas. Oral Dis 2010;16:774-80.
Shiga H, Rasmussen AA, Johnston PG, Langmacher M, Baylor A, Lee M, et al. Prognostic value of c-erbB2 and other markers in patients treated with chemotherapy for recurrent head and neckcancer. Head Neck 2000;22:599-608.
Yu D, Wang SS, Dulski KM, Tsai CM, Nicolson GL, Hung MC. c-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction ofmetastasis-associated properties. Cancer Res 1994;54:3260-6.
Pastuszewski W, Dziegiel P, Krecicki T, Podhorska- Okolow M, Ciesielska U, et al. Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer. Anticancer Res 2007;27:335-42.
Acikalin MF, Oner U, Tel N, Paşaoğlu O, Cakli H, Colak E. Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treatedby total laryngectomy. Eur Arch Otorhinolaryngol 2004;261:376-80.
Cordes C, Münzel AK, Rudolph P, Hoffmann M, Leuschner I, Gottschlich S. Immunohistochemical staining of Ki-67 using the monoclonal antibody Ki-s11 is a prognostic indicator forlaryngeal squamous cell carcinoma. Anticancer Res 2009;29:1459-65.
Lu SM, Yu L, Tian JJ, Ma JK, Li JF, Xu W, et al. Twist modulates lymphangiogenesis and correlates with lymph node metastasis in supraglottic carcinoma. Chin Med J (Engl) 2011;124:1483-7.
Lazaris ACh, Rigopoulou A, Tseleni-Balafouta S, Kavantzas N, Thimara I, Zorzos HS, et al. Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma. Histol Histopathol 2002;17:131-8.
Sarafoleanu D, Postelnicu V, Iosif C, Manea C, Sarafoleanu C. The role of p53, PCNA and Ki-67 as outcome predictors in the treatment of laryngeal cancer. J Med Life 2009;2:219-26.
Izawa H, Yonemitsu N, Shin T, Sugihara H. Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cellcarcinomas and dysplasia. Auris Nasus Larynx 1999;26:317-30.
Calli C, Calli A, Pinar E, Oncel S, Demirtaşoğlu F. Expression of Ki-67 and p53 in laryngeal squamous cell carcinomas. Kulak Burun Bogaz Ihtis Derg 2005;15:9-13.
Sittel C, Eckel HE, Damm M, von Pritzbuer E, Kvasnicka HM. Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma. Laryngoscope 2000;110:1012-7.