p27Kip1 expression as a prognostic marker for squamous cell carcinoma of the head and neck (Review)

Reis De Almeida,Miguel; Pérez‑Sayáns,Mario; Suárez‑Peñaranda,José  Manuel; Somoza-Martín,José   Manuel; García‑García,Abel

doi:10.3892/ol.2015.3726

p27Kip1 expression as a prognostic marker for squamous cell carcinoma of the head and neck (Review)

Authors:
- Miguel Reis De Almeida
- Mario Pérez‑Sayáns
- José Manuel Suárez‑Peñaranda
- José Manuel Somoza-Martín
- Abel García‑García
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Affiliations: Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Health Research Institute of Santiago (IDIS), Santiago de Compostela, A Coruña, Spain, Department of Pathology and Forensic Sciences, University Hospital and School of Medicine of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
Published online on: September 18, 2015 https://doi.org/10.3892/ol.2015.3726
Pages: 2675-2682
Copyright: © Reis De Almeida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Regulation of the cell cycle is essential for carcinogenesis. The cell cycle is controlled by cyclin-dependent kinases (CDKs), which are upregulated by cyclins and downregulated by CDK inhibitors (CDKIs). Decreased p27Kip1 expression has been associated with survival rate, tumor size, histological differentiation and the presence of lymph node metastasis in patients with various types of cancer. The aim of the current study is to provide a literature review on the association between p27Kip1 expression and the clinical and pathological aspects of head and neck squamous cell carcinoma (HNSCC), and the expression of other CDKIs of the Cip/Kip family and cyclins. Throughout the literature, different methodologies were used to determine the immunohistochemical expression of p27Kip1; thus, results concerning p27Kip1 expression in HNSCC vary widely. However, it has now been confirmed that p27Kip1 is underexpressed in SCC cells. p27 may be a promising marker for determining the prognosis of HNSCC, despite the marked variability of the results obtained. An association between p27 expression and survival rate, time to recurrence and tumor stage has been observed. Based on the information currently available, it is premature to recommend the analysis of p27Kip1 expression in guiding HNSCC treatment planning. However, although relatively unstudied, the correlation between p27Kip1 expression and other tumor suppressor genes may turn out to be important in determining the prognosis of HNSCC. Further prospective studies utilizing standardized laboratory methodologies and statistics that facilitate meta-analyses are required to confirm this proposal.

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1	Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar : PubMed/NCBI
2	Warnakulasuriya S: Living with oral cancer: Epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol. 46:407–410. 2010. View Article : Google Scholar : PubMed/NCBI
3	Perez-Ordoñez B, Beauchemin M and Jordan RC: Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol. 59:445–453. 2006. View Article : Google Scholar : PubMed/NCBI
4	Pérez-Sayáns M, Somoza-Martin JM, Barros-Angueira F, Reboiras-Lopez MD, Gándara Rey JM and Garcia-García A: Genetic and molecular alterations associated with oral squamous cell cancer (Review). Oncol Rep. 22:1277–1282. 2009. View Article : Google Scholar : PubMed/NCBI
5	Todd R, Hinds PW, Munger K, Rustgi AK, Opitz OG, Suliman Y and Wong DT: Cell cycle dysregulation in oral cancer. Crit Rev Oral Biol Med. 13:51–61. 2002. View Article : Google Scholar : PubMed/NCBI
6	Patel V, Jakus J, Harris CM, Ensley JF, Robbins KC and Yeudall WA: Altered expression and activity of G1/S cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck. Int J Cancer. 73:551–555. 1997. View Article : Google Scholar : PubMed/NCBI
7	Sherr CJ and Roberts JM: Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9:1149–1163. 1995. View Article : Google Scholar : PubMed/NCBI
8	Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 75:805–816. 1993. View Article : Google Scholar : PubMed/NCBI
9	Pérez-Sayáns M, Suárez-Peñaranda JM, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM and García-García A: p16 (INK4a)/CDKN2 expression and its relationship with oral squamous cell carcinoma is our current knowledge enough? Cancer Lett. 306:134–141. 2011. View Article : Google Scholar : PubMed/NCBI
10	Pérez-Sayáns M, Suárez-Peñaranda JM, Gayoso-Diz P, et al: The role of p21Waf1/CIP1 as a Cip/Kip type cell-cycle regulator in oral squamous cell carcinoma (Review). Med Oral Patol Oral Cir Bucal. 18:e219–e225. 2013. View Article : Google Scholar : PubMed/NCBI
11	Toyoshima H and Hunter T: p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 78:67–74. 1994. View Article : Google Scholar : PubMed/NCBI
12	Migita T, Oda Y, Naito S and Tsuneyoshi M: Low expression of p27 (Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma. Cancer. 94:973–979. 2002. View Article : Google Scholar : PubMed/NCBI
13	Zhuang Y, Yin HT, Yin XL, Wang J and Zhang DP: High p27 expression is associated with a better prognosis in east Asian non-small cell lung cancer patients. Clin Chim Acta. 412:2228–2231. 2011. View Article : Google Scholar : PubMed/NCBI
14	Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K and Yasumoto K: Significance of immunohistochemical expression of p27 and involucrin as the marker of cellular differentiation of squamous cell carcinoma of the esophagus. Oncology. 71:402–410. 2006. View Article : Google Scholar : PubMed/NCBI
15	Kouvaraki M, Gorgoulis VG, Rassidakis GZ, Liodis P, Markopoulos C, Gogas J and Kittas C: High expression levels of p27 correlate with lymph node status in a subset of advanced invasive breast carcinomas: Relation to E-cadherin alterations, proliferative activity and ploidy of the tumors. Cancer. 94:2454–2465. 2002. View Article : Google Scholar : PubMed/NCBI
16	Kudo Y, Kitajima S, Ogawa I, Miyauchi M and Takata T: Down-regulation of Cdk inhibitor p27 in oral squamous cell carcinoma. Oral Oncol. 41:105–116. 2005. View Article : Google Scholar : PubMed/NCBI
17	Kudo Y, Takata T, Yasui W, Ogawa I, Miyauchi M, Takekoshi T, Tahara E and Nikai H: Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is an indicator of malignant behavior in oral squamous cell carcinoma. Cancer. 83:2447–2455. 1998. View Article : Google Scholar : PubMed/NCBI
18	Fujieda S, Inuzuka M, Tanaka N, Sunaga H, Fan GK, Ito T, Sugimoto C, Tsuzuki H and Saito H: Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma. Int J Cancer. 84:315–320. 1999. View Article : Google Scholar : PubMed/NCBI
19	Jordan RC, Bradley G and Slingerland J: Reduced levels of the cell-cycle inhibitor p27Kip1 in epithelial dysplasia and carcinoma of the oral cavity. Am J Pathol. 152:585–590. 1998.PubMed/NCBI
20	Ito R, Yasui W, Ogawa Y, Toyosawa S, Tahara E and Ijuhin N: Reduced expression of cyclin-dependent kinase inhibitor p27 (Kip1) in oral malignant tumors. Pathobiology. 67:169–173. 1999. View Article : Google Scholar : PubMed/NCBI
21	Mineta H, Miura K, Suzuki I, Takebayashi S, Amano H, Araki K, Harada H, Ichimura K, Wennerberg JP and Dictor MR: Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma. Cancer. 85:1011–1017. 1999. View Article : Google Scholar : PubMed/NCBI
22	Schoelch ML, Regezi JA, Dekker NP, Ng IO, McMillan A, Ziober BL, Le QT, Silverman S and Fu KK: Cell cycle proteins and the development of oral squamous cell carcinoma. Oral Oncol. 35:333–342. 1999. View Article : Google Scholar : PubMed/NCBI
23	Saito T, Nakajima T and Mogi K: Immunohistochemical analysis of cell cycle-associated proteins p16, pRb, p53, p27 and Ki-67 in oral cancer and precancer with special reference to verrucous carcinomas. J Oral Pathol Med. 28:226–232. 1999. View Article : Google Scholar : PubMed/NCBI
24	Venkatesan TK, Kuropkat C, Caldarelli DD, Panje WR, Hutchinson JC Jr, Chen S and Coon JS: Prognostic significance of p27 expression in carcinoma of the oral cavity and oropharynx. Laryngoscope. 109:1329–1333. 1999. View Article : Google Scholar : PubMed/NCBI
25	Kudo Y, Takata T, Ogawa I, Zhao M, Sato S, Takekoshi T, Miyauchi M and Nikai H: Reduced expression of p27 (Kip1) correlates with an early stage of cancer invasion in oral squamous cell carcinoma. Cancer Lett. 151:217–222. 2000. View Article : Google Scholar : PubMed/NCBI
26	Kapranos N, Stathopoulos GP, Manolopoulos L, Kokka E, Papadimitriou C, Bibas A, Yiotakis J and Adamopoulos G: P53, p21 and p27 protein expression in head and neck cancer and their prognostic value. Anticancer Res. 21:521–528. 2001.PubMed/NCBI
27	Kudo Y, Kitajima S, Sato S, Miyauchi M, Ogawa I and Takata T: High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas. Cancer Res. 61:7044–7047. 2001.PubMed/NCBI
28	Harada K, Supriatno, Yoshida H and Sato M: Low p27Kip1 expression is associated with poor prognosis in oral squamous cell carcinoma. Anticancer Res. 22:2985–2989. 2002.PubMed/NCBI
29	Kuo MY, Hsu HY, Kok SH, Kuo RC, Yang H, Hahn LJ and Chiang CP: Prognostic role of p27 (Kip1) expression in oral squamous cell carcinoma in Taiwan. Oral Oncol. 38:172–178. 2002. View Article : Google Scholar : PubMed/NCBI
30	Shintani S, Mihara M, Nakahara Y, Kiyota A, Ueyama Y, Matsumura T and Wong DT: Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity. Oral Oncol. 38:235–243. 2002. View Article : Google Scholar : PubMed/NCBI
31	Kuropkat C, Venkatesan TK, Caldarelli DD, Panje WR, Hutchinson J, Preisler HD, Coon JS and Werner JA: Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx. Auris Nasus Larynx. 29:165–174. 2002. View Article : Google Scholar : PubMed/NCBI
32	Choi HR, Tucker SA, Huang Z, Gillenwater AM, Luna MA, Batsakis JG and El-Naggar AK: Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis. Int J Oncol. 22:409–414. 2003.PubMed/NCBI
33	Shintani S, Li C, Mihara M, Hino S, Nakashiro K and Hamakawa H: Skp2 and Jab1 expression are associated with inverse expression of p27 (KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology. 65:355–362. 2003. View Article : Google Scholar : PubMed/NCBI
34	Harada K, Supriatno, Yamamoto S, Kawaguchi S, Yoshida H and Sato M: Cepharanthine exerts antitumor activity on oral squamous cell carcinoma cell lines by induction of p27Kip1. Anticancer Res. 23:1441–1448. 2003.PubMed/NCBI
35	Kitajima S, Kudo Y, Ogawa I, Bashir T, Kitagawa M, Miyauchi M, Pagano M and Takata T: Role of Cks1 overexpression in oral squamous cell carcinomas: Cooperation with Skp2 in promoting p27 degradation. Am J Pathol. 165:2147–2155. 2004. View Article : Google Scholar : PubMed/NCBI
36	Rodolico V, Barresi E, Di Lorenzo R, Leonardi V, Napoli P, Rappa F and Di Bernardo C: Lymph node metastasis in lower lip squamous cell carcinoma in relation to tumour size, histologic variables and p27Kip1 protein expression. Oral Oncol. 40:92–98. 2004. View Article : Google Scholar : PubMed/NCBI
37	Rodolico V, Aragona F, Cabibi D, Di Bernardo C, Di Lorenzo R, Gebbia N, Gulotta G, Leonardi V and Ajello F: Overexpression of cyclin D1 and interaction between p27Kip1 and tumour thickness predict lymph node metastases occurrence in lower lip squamous cell carcinoma. Oral Oncol. 41:268–275. 2005. View Article : Google Scholar : PubMed/NCBI
38	Fillies T, Woltering M, Brandt B, Van Diest JP, Werkmeister R, Joos Uz and Buerger H: Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell carcinomas. Oncol Rep. 17:355–359. 2007.PubMed/NCBI
39	Queiroz AB, Focchi G, Dobo C, Gomes TS, Ribeiro DA and Oshima CT: Expression of p27, p21 (WAF/Cip1) and p16 (INK4a) in normal oral epithelium, oral squamous papilloma and oral squamous cell carcinoma. Anticancer Res. 30:2799–2803. 2010.PubMed/NCBI
40	Martín-Ezquerra G, Salgado R, Toll A, Baró T, Mojal S, Yébenes M, Garcia-Muret MP, Solé F, Quitllet FA, Espinet B and Pujol RM: CDC28 protein kinase regulatory subunit 1B (CKS1B) expression and genetic status analysis in oral squamous cell carcinoma. Histol Histopathol. 26:71–77. 2011.PubMed/NCBI
41	Gao L, Huang S, Ren W, Zhao L, Li J, Zhi K, Zhang Y, Qi H and Huang C: Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27. Med Oncol. 29:2499–2504. 2012. View Article : Google Scholar : PubMed/NCBI
42	Monteiro LS, Diniz-Freitas M, Garcia-Caballero T, Warnakulasuriya S, Forteza J and Fraga M: Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma. J Oral Pathol Med. 41:559–567. 2012.PubMed/NCBI
43	Perisanidis C, Perisanidis B, Wrba F, Brandstetter A, El Gazzar S, Papadogeorgakis N, Seemann R, Ewers R, Kyzas PA and Filipits M: Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1 and Ki67 in oral and oropharyngeal squamous cell carcinoma. J Oral Pathol Med. 41:40–46. 2012. View Article : Google Scholar : PubMed/NCBI
44	Canzonieri V, Barzan L, Franchin G, Vaccher E, Talamini R, Sulfaro S and Baldassarre G: Alteration of G1/S transition regulators influences recurrences in head and neck squamous carcinomas. J Cell Physiol. 227:233–238. 2012. View Article : Google Scholar : PubMed/NCBI
45	Zhang M, Li J, Wang L, Tian Z, Zhang P, Xu Q, Zhang C, Wei F and Chen W: Prognostic significance of p21, p27 and survivin protein expression in patients with oral squamous cell carcinoma. Oncol Lett. 6:381–386. 2013.PubMed/NCBI
46	Shintani S, Li C, Mihara M, Hino S, Nakashiro K and Hamakawa H: Skp2 and Jab1 expression are associated with inverse expression of p27 (KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology. 65:355–362. 2003. View Article : Google Scholar : PubMed/NCBI
47	Fan GK, Chen J, Ping F and Geng Y: Immunohistochemical analysis of P57 (kip2), p53 and hsp60 expressions in premalignant and malignant oral tissues. Oral Oncol. 42:147–153. 2006. View Article : Google Scholar : PubMed/NCBI
48	Pignataro L, Sambataro G, Pagani D and Pruneri G: Clinico-prognostic value of D-type cyclins and p27 in laryngeal cancer patients: A review. Acta Otorhinolaryngol Ital. 25:75–85. 2005.PubMed/NCBI