Expression of p53, p21 ^CIP1/WAF1 and eIF4E in the adjacent tissues of oral squamous cell carcinoma: establishing the molecular boundary and a cancer progression model

Abstract

Surgical removal of apparently normal tissue adjacent to oral squamous cell carcinoma (OSCC) tumors could improve patient outcomes. OSCC is the most common oral cancer and survival rates are only around 50%, mainly due to local recurrence. Long-Jiang Li, at Sichuan University, Chengdu, China, and colleagues, examined 50 biopsy samples from patients treated for OSCC and found that tissues up to 2 cm away from the visible border of the tumor could be pre-cancerous. A gradual decrease in the expression of cancer-related molecules from the tumor to surrounding tissue suggests that some cells, despite their normal appearance, have begun to transform into tumor-forming cells. By determining the molecular boundary of OSCC tumors, these findings help to establish a safer surgical margin which fully removes precancerous tissue and thus lowers the risk of recurrence.

Keywords

eIF4E / molecular boundary / oral squamous cell carcinoma / p21 / p53

References

[1] McDowell JD. An overview of epidemiology and common risk factors for oral squamous cell carcinoma. Otolaryngol Clin North Am, 2006, 39(2): 277-294.

[2] Yanamoto S, Yamada S, Takahashi H. Clinicopathological risk factors for local recurrence in oral squamous cell carcinoma. Int J Oral Maxillofac Surg, 2012, 41(10): 1195-1200.

[3] Guillemaud JP, Patel RS, Goldstein DP. Prognostic impact of intraoperative microscopic cut-through on frozen section in oral cavity squamous cell carcinoma. J Otolaryngol Head Neck Surg, 2010, 39(4): 370-377.

[4] Brandwein-Gensler M, Teixeira MS, Lewis CM. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol, 2005, 29(2): 167-178.

[5] Lyons AJ, Jones J. Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg, 2007, 36(8): 671-679.

[6] Jacobs JR, Ahmad K, Casiano R. Implications of positive surgical margins. Laryngoscope, 1993, 103(1 Pt 1): 64-68.

[7] Dolcetti R, Doglioni C, Maestro R. 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(2): 178-182.

[8] Curran AJ, St Denis K, Irish J. Telomerase activity in oral squamous cell carcinoma. Arch Otolaryngol Head Neck Surg, 1998, 124(7): 784-788.

[9] Gale N, Plich BZ, Sidransky D. Tumours of the hypopharynx, larynx and trachea (Epithelial precursor lesions). World Health Organization Classification of Tumours Pathology & Genetics Head and Neck Tumours International Agency for Research on Cancer (IARC), 2005 Lyon 140-143.

[10] Stark AM, Hugo HH, Tscheslog H. p53, BCL-2 and BAX in non-small cell lung cancer brain metastases: a comparison of real-time RT-PCR, ELISA and immunohistochemical techniques. Neurol Res, 2007, 29(5): 435-440.

[11] Schindlbeck C, Hantschmann P, Zerzer M. Prognostic impact of KI67, p53, human epithelial growth factor receptor 2, topoisomerase IIalpha, epidermal growth factor receptor, and nm23 expression of ovarian carcinomas and disseminated tumor cells in the bone marrow. Int J Gynecol Cancer, 2007, 17(5): 1047-1055.

[12] Chiou WY, Lin HY, Hsu FC. Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence. Radiat Oncol, 2010, 5: 79.

[13] Ota Y, Aoki T, Karakida K. Determination of deep surgical margin based on anatomical architecture for local control of squamous cell carcinoma of the buccal mucosa. Oral Oncol, 2009, 45(7): 605-609.

[14] Ngoi SS, Staiano-Coico L, Godwin TA. Abnormal DNA ploidy and proliferative patterns in superficial colonic epithelium adjacent to colorectal cancer. Cancer, 1990, 66(5): 953-959.

[15] Hoffmann TK, Bier H, Donnenberg AD. p53 as an immunotherapeutic target in head and neck cancer. Adv Otorhinolaryngol, 2005, 62: 151-160.

[16] Carlos de Vicente J, Junquera Gutiérrez LM, Zapatero AH. Prognostic significance of p53 expression in oral squamous cell carcinoma without neck node metastases. Head Neck, 2004, 26(1): 22-30.

[17] Heah KG, Hassan MI, Huat SC. p53 expression as a marker of microinvasion in oral squamous cell carcinoma. Asian Pac J Cancer Prev, 2011, 12(4): 1017-1022.

[18] Kato K, Kawashiri S, Yoshizawa K. Expression form of p53 and PCNA at the invasive front in oral squamous cell carcinoma: correlation with clinicopathological features and prognosis. J Oral Pathol Med, 2011, 40(9): 693-698.

[19] Perisanidis C, Perisanidis B, Wrba F. Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 in oral and oropharyngeal squamous cell carcinoma. J Oral Pathol Med, 2012, 41(1): 40-46.

[20] Allegra E, Puzzo L, Cutrona D. p53 overexpression on the resection margins as a marker of local recurrence in glottic T1a carcinoma. Acta Otorhinolaryngol Ital, 2003, 23(6): 454-458.

[21] el-Deiry WS, Tokino T, Velculescu VE. WAF1, a potential mediator of p53 tumor suppression. Cell, 1993, 75(4): 817-825.

[22] Harper JW, Adami GR, Wei N. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell, 1993, 75(4): 805-816.

[23] Gartel AL, Radhakrishnan SK. Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res, 2005, 65(10): 3980-3985.

[24] Bedelbaeva K, Snyder A, Gourevitch D. Lack of p21 expression links cell cycle control and appendage regeneration in mice. Proc Natl Acad Sci U S A, 2010, 107(13): 5845-5850.

[25] De Benedetti A, Graff JR. eIF-4E expression and its role in malignancies and metastases. Oncogene, 2004, 23(18): 3189-3199.

[26] Nathan CO, Franklin S, Abreo FW. Analysis of surgical margins with the molecular marker eIF4E: a prognostic factor in patients with head and neck cancer. J Clin Oncol, 1999, 17(9): 2909-2914.

[27] Sunavala-Dossabhoy G, Palaniyandi S, Clark C. Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer. Laryngoscope, 2011, 121(10): 2136-2141.

[28] Sorrells DL Jr, Ghali GE, de Benedetti A. Progressive amplification and overexpression of the eukaryotic initiation factor 4E gene in different zones of head and neck cancers. J Oral Maxillofac Surg, 1999, 57(3): 294-299.

[29] Franklin S, Pho T, Abreo FW. Detection of the proto-oncogene eIF4E in larynx and hypopharynx cancers. Arch Otolaryngol Head Neck Surg, 1999, 125(2): 177-182.

[30] Nathan CO, Amirghahri N, Rice C. Molecular analysis of surgical margins in head and neck squamous cell carcinoma patients. Laryngoscope, 2002, 112(12): 2129-2140.

[31] Babichenko II, Rabinovich OF, Ivina AA et al . [Papillomavirus in the genesis of oral leukoplakia .] Arkh Patol 2014; 76 ( 1 ): 32 – 36 . Russian .

[32] Myoung H, Kim MJ, Lee JH. Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients. Int J Oral Maxillofac Surg, 2006, 35(11): 1005-1010.

[33] Akino T, Hida K, Hida Y. Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors. Am J Pathol, 2009, 175(6): 2657-2667.

[34] Romics I, Bocsi J, Bach D. DNA content of prostatic cancer measured by flow cytometry in patients undergoing radical prostatectomy. Anticancer Res, 1995, 15(3): 1131-1134.

[35] Bignold LP. Mutation, replicative infidelity of DNA and aneuploidy sequentially in the formation of malignant pleomorphic tumors. Histol Histopathol, 2007, 22(3): 321-326.

[36] Abou-Elhamd KE, Habib TN. The flow cytometric analysis of premalignant and malignant lesions in head and neck squamous cell carcinoma. Oral Oncol, 2007, 43(4): 366-372.

[37] Marur S, D'Souza G, Westra WH. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol, 2010, 11(8): 781-789.

[38] Kero K, Rautava J, Syrjänen K. Oral mucosa as a reservoir of human papillomavirus: point prevalence, genotype distribution, and incident infections among males in a 7-year prospective study. Eur Urol, 2012, 62(6): 1063-1070.

[39] Ruttkay-Nedecky B, Jimenez Jimenez AM, Nejdl L. Relevance of infection with human papillomavirus: the role of the p53 tumor suppressor protein and E6/E7 zinc finger proteins (Review). Int J Oncol, 2013, 43(6): 1754-1762.

[40] Huibregtse JM, Scheffner M, Howley PM. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J, 1991, 10(13): 4129-4135.

[41] Gillison ML, D'Souza G, Westra W. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst, 2008, 100(6): 407-420.