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Open Access 01-12-2006 | Research article

Prognostic value of p27^Kip1expression in Basaloid Squamous Cell Carcinoma of the larynx

Authors: Grazia Salerno, Dolores Di Vizio, Stefania Staibano, Giampiero Mottola, Giuseppe Quaremba, Massimo Mascolo, Vieri Galli, Gaetano De Rosa, Luigi Insabato

Published in: BMC Cancer | Issue 1/2006

Abstract

Background

Very few reports have investigated the role of cell cycle regulators as biomarkers in Basaloid Squamous Cell Carcinoma (BSCC) of the larynx, a definite morphologic, uncommon, very aggressive variant of squamous cell carcinoma. Lower expression of Ki67/Mib-1, a proliferation marker highly expressed in the majority of tumours, and p53, a tumour suppressor protein that can induce an arrest of the G1-S transition, was related to a better prognosis in laryngeal BSCC. In the head and neck, p27^kip1, a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors, has emerged as an independent prognostic factor, able to identify low-expressing tumours with unfavourable course. Up to date the role of this protein was never studied in BSCC. Aim of our study was to investigate the potential prognostic value of p27^kip1 levels and their correlation with Ki67/Mib-1 and p53 expression in BSCC of the larynx.

Methods

The retrospective study group consisted of 15 male and 1 female patients, affected by laryngeal BSCC, ranging in age from 44 to 69 years (mean 58). The tumour originated from the supraglottis in thirtheen cases and from the glottis in the remaining three. Ten patients had metastatic cervical lymph nodes at presentation and were classified as N+. Post surgical stage was IV in four patients, III in nine, II in two cases and I in the remaining one. Follow-up ranged from a minimum of 5 months up to 9 years. Paraffin-embedded tissue sections of each laryngeal tumour were analyzed for p27^kip, Ki67/Mib-1 and p53 expression by immunohistochemistry.

Results

The immunohistochemical study showed p27^kip1 expression in 40% of the patients with no evidence of disease (NED) and in none (0%) of the patients dead of disease (DOD), whilst p53 was expressed in 60% of patients in NED status and in 90% of patients in DOD status. Ki67/Mib-1 was positive in 80% of NED patients and in 100% of DOD patients. At multivariate analysis, performed by means of Discriminant analysis, low levels of p27^kip1 expression significantly correlated with poor prognosis (P < 0.05).

Conclusion

p27^kip1 protein has been shown to be a significant independent prognostic factor in laryngeal SCC. In our series of laryngeal BSCC the resulting data seem to confirm the clinical prognostic relevance of p27^kip1 low expression, which directly correlated with biological aggressiveness and consequent shortened survival.

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Wain SL, Kier R, Vollmer RT, Bossen EH: Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. Hum Pathol. 1986, 17: 1158-1166.CrossRefPubMed

Luna MA, el Naggar A, Parichatikanond P, Weber RS, Batsakis JG: Basaloid squamous carcinoma of the upper aero digestive tract. Clinicopathologic and DNA flow cytometric analysis. Cancer. 1990, 66: 537-542. 10.1002/1097-0142(19900801)66:3<537::AID-CNCR2820660322>3.0.CO;2-J.CrossRefPubMed

Batsakis JG, El Naggar A: Basaloid-squamous carcinomas of the upper aereodigestive tracts. Ann Otol Rhinol Laryngol. 1989, 98: 919-920.CrossRefPubMed

Owonikoko T, Loberg C, Gabert HE, Sarbia M: Comparative analysis of basaloid and typical squamous cell carcinoma of the oesophagus: A molecular biological and immunohistochemical study. J Pathol. 2001, 193: 155-161. 10.1002/1096-9896(2000)9999:9999<::AID-PATH758>3.0.CO;2-D.CrossRefPubMed

Campman SC, Gandour-Edwards RF, Sykes JN: Basaloid squamous cell carcinoma of the head and neck. Report of a case in the anterior floor of the mouth. Arch Path Lab Med. 1994, 118: 1229-1232.PubMed

Banks ER, Frierson HF, Mills SE, George E, Zarbo RJ, Swanson PE: Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol. 1992, 16: 939-946.CrossRefPubMed

Klijanienko J, el-Naggar A, Ponzio-Prion A, Marandes P, Micheau C, Caillaud JM: Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1993, 119: 887-890.CrossRefPubMed

Raslan WF, Barnes L, Krause JR, Contis L, Killeen R, Kapadia SB: Basaloid squamous cell carcinoma of the head and neck: a clinicopathologic and flow cytometric study of 10 new cases with review of the English literature. Am J Otolaryngol. 1994, 15: 204-211. 10.1016/0196-0709(94)90006-X.CrossRefPubMed

Paulino AF, Singh B, Shah JP, Huvos AG: Basaloid squamous cell carcinoma of the head and neck. Laryngoscope. 2000, 110: 1479-1482. 10.1097/00005537-200009000-00013.CrossRefPubMed

10.

Erdamar B, Suoglu Y, Sirin M, Karatay C, Katircioglu S, Kiyak E: Basaloid squamous cell carcinoma of the supraglottic larynx. Eur Arch Otorhinolaryngol. 2000, 257: 154-7. 10.1007/s004050050213.CrossRefPubMed

11.

Ereno C, Lopez JI, Sanchez JM, Toledo JD: Basaloid-squamous cell carcinoma of the larynx and hypopharynx. A clinicopathologic study of 7 cases. Pathol Res Pract. 1994, 190: 186-193.CrossRefPubMed

12.

Ferlito A, Altavilla G, Rinaldo A, Doglioni C: Basaloid squamous cell carcinoma of the larynx and hypopharynx. Ann Otol Rhinol Laryngol. 1997, 106: 1024-1035.CrossRefPubMed

13.

Eryilmaz A, Gocer C, Acar A, Dagli M, Albayrak L: Basaloid squamous cell carcinoma of the larynx. J Laryngol Otol. 2002, 116: 52-53. 10.1258/0022215021910131.CrossRefPubMed

14.

Sato M, Horiuchi M, Ogata T, Yamazaki M, Sakai M, Kato Y, Shimamura K: Basaloid squamous carcinoma of the larynx: report of a case. Auris Nasus Larynx. 1997, 24: 417-422. 10.1016/S0385-8146(97)10005-0.CrossRefPubMed

15.

Sheen TS, Chang YL, Ko JY, Wu CT, Lee SY: Basaloid squamous cell carcinoma of the larynx. Otolaryngol Head Neck Surg. 1999, 121: 155-161. 10.1016/S0194-5998(99)70074-4.CrossRef

16.

Bracero F, Gamiz MJ, Soldado L, Conde JM, Redondo M, Gonzales MA, Lopez Garrido J, Esteban F: Hypopharynx and larynx basaloid squamous cell carcinoma: our experience with 6 cases. Acta Otorrinolaringol Esp. 2001, 52: 229-236.CrossRefPubMed

17.

Prasad KC, Kaniyur V, Devan PP, Kedakalathil J: Basaloid squamous cell carcinoma of the larynx: Report of a case. Ear Nose Throat J. 2002, 81: 254-255.PubMed

18.

Bahar G, Feinmesser R, Popovtzer A, Ulanovsky D, Nageris B, Marshak G, Feinmesser M: Basaloid squamous carcinoma of the larynx. Am J Otolaryngol. 2003, 24: 204-208. 10.1016/S0196-0709(03)00004-8.CrossRefPubMed

19.

Erisen LM, Coskun H, Ozuysal S, Basut O, Onart S, Hizalan I: Basaloid squamous cell carcinoma of the larynx: a report of four new cases. Laryngoscope. 2004, 114 (7): 1179-1183. 10.1097/00005537-200407000-00009.CrossRefPubMed

20.

Kleist B, Bankau A, Lorenz G, Jager B, Poetsch M: Different risk factors in basaloid and common squamous head and neck cancer. Laryngoscope. 2004, 114: 1063-1068. 10.1097/00005537-200406000-00020.CrossRefPubMed

21.

Marioni G, Gaio E, Giacomelli L, Marchese-Ragona R, Staffieri C, Staffieri A, Marino F: Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma. Acta Otolaryngol. 2005, 125: 307-311. 10.1080/00016480410023047.CrossRefPubMed

22.

Rodriguez Tojo MJ, Garcia Cano FJ, Infante Sanchez JC, Velazquez Fernandez E, Aguirre Urizar JM: Immunoexpression of p53, Ki-67 and E-cadherin in basaloid squamous cell carcinoma of the larynx. Clin Transl Oncol. 2005, 7: 110-114.CrossRefPubMed

23.

Ozturk O, Sari M, Inanli S, Kara EK: Basaloid squamous cell of the larynx: a case report. Kulak Burun Bogaz Ihtis Derg. 2005, 15: 125-129.PubMed

24.

Alkan S, Coskun BU, Ugur S, Basak T, Dadas B: Basaloid squamous cell carcinoma of the larynx. Auris Nasus Larynx. 2006, 33: 71-74. 10.1016/j.anl.2005.07.017.CrossRefPubMed

25.

Vielba R, Bilbao J, Ispizua A, Zabalza I, Alfaro J, Rezolo R, Moreno E, Elorriaga J, Alonso J, Barojo A, de la Hz C: p53 and Cyclin D1 as prognostic factors in squamous cell carcinoma of the larynx. Laryngoscope. 2003, 113: 167-172. 10.1097/00005537-200301000-00031.CrossRefPubMed

26.

Hirai T, Hayashi K, Takumida M, Hirakawa K, Yajin K: Reduced expression f p27 is correlated with progression in precancerous lesions of the larynx. Auris Nasus Larynx. 2003, 30: 163-168. 10.1016/S0385-8146(03)00007-5.CrossRefPubMed

27.

Pruneri G, Pignataro L, Carboni N, Buffa N, Di Finizio D, Cesana BM, Neri A: Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer. J Clin Oncol. 1999, 17: 3150-3159.PubMed

28.

Fan GK, Fujieda S, Sunaga H, Tsuzuki H, Ito N, Sato H: Expression of p27 is associated with progression and prognosis in laryngeal cancer. Laryngoscope. 1999, 109: 815-820. 10.1097/00005537-199905000-00025.CrossRefPubMed

29.

Qin XL, Guo QH, Zheng H, Zheng Y: p27 protein expression and its significance in human laryngeal carcinoma. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2000, 14 (12): 533-535.PubMed

30.

Tamura N, Dong Y, Sui L, Tai Y, Sugimoto K, Nagahata S, Tokuda M: Cyclin-dependent kinase inhibitor p27 is related to cell proliferation and prognosis in laryngeal squamous cell carcinomas. J Laryngol Otol. 2001, 115: 400-406. 10.1258/0022215011907749.CrossRefPubMed

31.

Kapranos N, Stathopoulos GP, Manolopulos L, Kokka E, Papadimitriou C, Bibas A, Yiotakis J, Adamopoulos G: p53, p21 and p27 protein expression in head and neck cancer: their prognostic significance. Anticancer Res. 2001, 21: 521-8.PubMed

32.

Korkmaz H, Du W, Yoo GH, Enamorado II, Lin HS, Adsay V, Kewson D, Ensley JF, Shibuya TY, Jacob JR, Kim H: Prognostic significance of G1 cell-cycle inhibitor in early laryngeal cancer. Am J Otolaryngol. 2005, 26: 77-82. 10.1016/j.amjoto.2004.08.001.CrossRefPubMed

33.

Pignataro L, Sambataro G, Pagani D, Pruneri G: Clinico-prognostic value of D-type cyclins and P27 in laryngeal cancer patients: a review. Acta Otorhinolaryngol Ital. 2005, 25 (2): 75-85.PubMedPubMedCentral

34.

Tsubochi H, Suzuki T, Suzuki S, Ohashi Y, Ishibashi S, Moriya T, Fujimura S, Sasano H: Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract. Anticancer Research. 2000, 20: 1205-1211.PubMed

35.

Akyol MU, Dursun A, Akyol G, Edaliota N: Proliferating cell nuclear antigen immunoreactivity and the presence of p53 mutation in basaloid squamous cell carcinoma of the larynx. Oncology. 1998, 55: 382-383. 10.1159/000011882.CrossRefPubMed

36.

Iamaroon A, Khemaleelakul U, Pongsiriwet S, Pintong J: Co-expression of p53 and Ki67 and lack of EBV expression in oral squamous cell carcinoma. J Oral Pathol Med. 2004, 33: 30-36. 10.1111/j.1600-0714.2004.00192.x.CrossRefPubMed

37.

Nakamura N, Yamamoto H, Yao T, Oda Y, Nishiyama K, Imamura M, Yamada T, Nawata H, Tsuneyoshi M: Prognostic significance of expressions of cell cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade. Hum Pathol. 2005, 36: 828-837. 10.1016/j.humpath.2005.03.012.CrossRefPubMed

38.

Hand DJ: Discrimination and Classification. 1977, John Wiley & Sons, New York

39.

Van der Geer JP: Introduction to multivariate analysis for the social sciences. 1971, W.H. Freeman, San Francisco

40.

Kendall M, Stuart A: The Advanced Theory of Statistics. 1977, MacMillan, New York

41.

Martin SA, Marks JE, Lee JY, Bauer WC, Ogura JH: Carcinoma of the pyriform sinus: predictors of TNM relapse and survival. Cancer . 1980, 46 (9): 1974-1981. 10.1002/1097-0142(19801101)46:9<1974::AID-CNCR2820460913>3.0.CO;2-A. 1CrossRefPubMed

42.

Spector JG, Sessions DG, Emami B, Simpson J, Haughey B, Fredrickson JM: Squamous cell carcinomas of the aryepiglottic fold: therapeutic result and long-term follow-up. Laryngoscope. 1995, 105: 734-746.CrossRefPubMed

43.

Yuen AP, Ho CM, Wei WI, Lam LK: Prognosis of recurrent laryngeal carcinoma after laryngectomy. Head Neck. 1995, 17: 526-530.CrossRefPubMed

44.

Jin YT, Kayser S, Kemp BL, Ordonez NG, Tucker SL, Clayman GL, Goepfert H, Luna MA, Batsakis Jg, el-Naggar AK: The prognostic significance of the biomarkers p21WAF1/CIP1, p53, and bcl-2 in laryngeal squamous cell carcinoma. Cancer. 1998, 82: 2159-2165. 10.1002/(SICI)1097-0142(19980601)82:11<2159::AID-CNCR10>3.0.CO;2-T.CrossRefPubMed

45.

Dolcetti R, Doglioni C, Maestro R, Gasparotto D, Barzan L, Pastore A, Romanelli M, Boiocchi M: p53 over-expression is an early event in the development of human squamous cell carcinoma of the larynx: genetic and prognostic implications. Int J Cancer. 1992, 52: 178-182.CrossRefPubMed

46.

Maestro R, Dolcetti R, Gasparotto D, Doglioni C, Pelucchi S, Barzan L, Grandi E, Boiocchi M: High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx. Oncogene. 1992, 7: 1159-1166.PubMed

47.

Liu M, Lawson G, Delos M, Jamart J, Chatelain B, Remacle M, Marbaix E: Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: comparison with clinical and radiologic examinations. Head Neck. 2003, 25: 280-288. 10.1002/hed.10218.CrossRefPubMed

48.

Chatrath P, Scott IS, Morris LS, Davies RJ, Rushbrook SM, Bird K, Vowler SL, Grant JW, Saeed IT, Howaed D, Laskey RA, Coleman N: Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions. Br J Cancer. 2003, 89 (6): 1048-1054. 10.1038/sj.bjc.6601234. 15CrossRefPubMedPubMedCentral

49.

Assimakopoulos D, Kolettas E, Zagorianakou N, Evangelou A, Skevas A, Agnantis NJ: Prognostic significance of p53 in the cancer of the larynx. Anticancer Res. 2000, 20: 3555-3564.PubMed

50.

Friedman M, Lim JW, Manders E, Schaffner AD, Kirschenbaum GL, Tanyeri HM, Caldarelli DD, Coon JS: Prognostic significance of Bcl-2 and p53 expression in advanced laryngeal squamous cell carcinoma. Head Neck. 2001, 23: 280-285. 10.1002/hed.1031.CrossRefPubMed

51.

Perez-Carro Rios A, Lozano Ramirez A, Garcia Caballero T, Labella Caballero T, Clemente Garcia A: An immunohistochemistry study of p53 in squamous cell carcinoma of the larynx. Acta Otorrinolaringol Esp. 2003, 54: 263-268.CrossRefPubMed

52.

Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, Scheithauer BW: p27: A multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999, 154: 313-323.CrossRefPubMedPubMedCentral

53.

Chiarle R, Fan Y, Piva R, Boggino H, Skolnik J, Novero D, Palestro G, De Wolf-Peeters C, Chilosi M, Pagano M, Inghirami G: S-phase kinase associated protein 2 expression in non-Hodgkin's Lymphoma inversely correlates with p27 expression and defines cells in S phase. Am J Pathol. 2002, 160: 1457-1466.CrossRefPubMedPubMedCentral

54.

Baldassare G, Belletti B, Bruni P, Boccia A, Trapasso F, Pentimalli F, Barone MV, Chiappetta G, Vento MT, Fusco A, Viglietto G: Overexpressed Cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells. J Clin Invest. 1999, 104: 865-874.CrossRef

55.

Jordan RC, Bradley G, Slingerland J: Reduced levels of the cell-cycle inhibitor p27Kip1 in epithelial displasia and carcinoma of the oral cavity. Am J Pathol. 1998, 152: 585-590.PubMedPubMedCentral

56.

Peters S, Hambek M, Gstottner W, Knecht R: Tissue microarrays. Value of immunohistochemical proliferation markers for serial investigations of head and neck cancer. HNO. 2004, 52: 409-12. 10.1007/s00106-004-1092-2.CrossRefPubMed

57.

Di Gennaro E, Barbarino M, Bruzzese F, De Lorenzo S, Caraglia M, Abbruzzese A, Avallone A, Comella P, Caponigro F, Pepe S, Budillon A: Critical role of both p27KIP1 and p21CIP1/WAF1 in the antiproliferative effect of ZD1839 (Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor, in head and neck squamous carcinoma cells. J Cell Physiol. 2003, 195: 139-150. 10.1002/jcp.10239.CrossRefPubMed

58.

Patel V, Lahusen T, Leethanakul C, Igishi T, Kremer M, Quintanilla-Martinez L, Ensley JF, Sausville EA, Gutkind JS, Senderowicz AM: Antitumor activity of UCN-01 in carcinoma of the head and neck is associated with altered expression of cyclin D3 and p27(kip1). Clin Cancer Res. 2002, 8: 3549-3560.PubMed

59.

Kudo Y, Kitajima S, Sato S, Ogawa I, Miyauchi M, Takata T: Transfection of p27 (Kip1) threonine residue 187 mutant type gene, which is not influenced by ubiquitin-mediated degradation, induces cell cycle arrest in oral squamous cell carcinoma cells. Oncology. 2002, 63: 398-404. 10.1159/000066222.CrossRefPubMed

60.

Koh TY, Park KH, Lee SG, Seol JG, Lee DW, Lee CT, Heo DS, Kim KH, Sung MW: Inhibitory effect of p27 KIP1 gene transfer in head and neck squamous cell carcinoma cell lines. Head Neck. 2003, 25: 44-49. 10.1002/hed.10166.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/146/prepub

Title: Prognostic value of p27Kip1expression in Basaloid Squamous Cell Carcinoma of the larynx
Authors: Grazia Salerno
Dolores Di Vizio
Stefania Staibano
Giampiero Mottola
Giuseppe Quaremba
Massimo Mascolo
Vieri Galli
Gaetano De Rosa
Luigi Insabato
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-6-146

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