Journal of Otolaryngology-Head & Neck Surgery | |
Prognostic utility of basaloid differentiation in oropharyngeal cancer | |
Hadi Seikaly3  Lakshmi Puttagunta1  Alexander C Klimowicz2  Ben Adam1  Vincent Biron3  Timothy Cooper3  | |
[1] Department of Laboratory Medicine & Pathology, University of Alberta, 5B2 University of Alberta Hospital, Edmonton, AB T6G 2B7, Canada;Department of Oncology, University of Calgary, Tom Baker Cancer Centre, 1331-29 Street NW, Calgary, AB T2N 4 N2, Canada;Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Alberta, 1E4 University of Alberta Hospital, Edmonton, AB T6G 2B7, Canada | |
关键词: Survival; Outcomes; Squamous cell carcinoma; Oropharynx; Eosin; Hematoxylin; p16; HPV; Basaloid differentiation; | |
Others : 861523 DOI : 10.1186/1916-0216-42-57 |
|
received in 2013-04-02, accepted in 2013-11-21, 发布年份 2013 | |
【 摘 要 】
Background
Human papillomavirus (HPV) is recognized as the key risk factor for a distinct subset of oropharyngeal squamous cell carcinoma. P16 is a reliable, sensitive surrogate marker for HPV and confers a positive prognostic advantage. Basaloid differentiation on hematoxylin and eosin (H&E) staining is anecdotally noted by some pathologists to be associated with p16 positivity. This association, however, has not been adequately quantified in the literature, nor has the prognostic implications of basaloid differentiation been described.
Objectives
1) To correlate the H&E staining feature of basaloid differentiation with p16 positivity in oropharyngeal cancer. 2) To investigate the prognostic utility of basaloid differentiation in oropharyngeal cancer survival.
Methods
Retrospective cross-sectional study of all patients diagnosed with and treated for oropharyngeal cancer at a single tertiary cancer center from 2002 to 2009. Tissue microarrays (TMAs) were generated from 208 oropharyngeal tumor specimens stained with H&E and immunohistochemical markers. These oropharyngeal TMAs were utilized in several previous publications. Samples were scored for basaloid differentiation by a pathologist blinded to the p16 result. A multivariate survival analysis with Cox-regression and Kaplan-Meier survival analysis was performed.
Results
In the 208 samples, basaloid differentiation correlated with p16 positivity (Spearman’s rho 0.435). Basaloid differentiation and p16 positivity were both independent predictors of improved survival. The 5 year disease specific survival (DSS) was 73% for p16 positive tumors and 35% for p16 negative tumors (p < 0.001). Similarly, the 5 year DSS of basaloid differentiated tumors was 74% compared to 41% for non-basaloid tumors (p = 0.001). Patients with p16 positive and basaloid differentiated tumors had the best survival outcomes with a 5 year DSS of 80%.
Conclusions
Basaloid differentiation is a feature on H&E which correlates with p16 positivity and is a simple, inexpensive, independent, positive prognostic indicator of comparable magnitude to p16 status. Due to the added prognostic value of basaloid differentiation, this feature should be routinely reported by qualified pathologists.
【 授权许可】
2013 Cooper et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140725002026190.pdf | 522KB | download | |
60KB | Image | download | |
51KB | Image | download | |
53KB | Image | download |
【 图 表 】
【 参考文献 】
- [1]Cardesa A, Nadal A: Carcinoma of the head and neck in the HPV era. Acta Dermatovenerol Alp Panonica Adriat 2011, 20(3):161-173.
- [2]El-Mofty SK, Patil S: Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006, 101(3):339-345.
- [3]Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000, 92(9):709-720.
- [4]Klussmann JP, Weissenborn SJ, Wieland U, et al.: Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 2001, 92(11):2875-2884.
- [5]El-Mofty SK, Lu DW: Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol 2003, 27(11):1463-1470.
- [6]Nichols AC, Faquin WC, Westra WH, et al.: HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg 2009, 140(2):228-234.
- [7]Westra WH: The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol 2009, 3(1):78-81.
- [8]Schache AG, Liloglou T, Risk JM, et al.: Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: Sensitivity, specificity, and prognostic discrimination. Clin Cancer Res 2011, 17(19):6262-6271.
- [9]Dufour X, Beby-Defaux A, Agius G, Lacau St Guily J: HPV and head and neck cancer. Eur Ann Otorhinolaryngol Head Neck Dis 2012, 129(1):26-31.
- [10]Lau HY, Brar S, Klimowicz AC, et al.: Prognostic significance of p16 in locally advanced squamous cell carcinoma of the head and neck treated with concurrent cisplatin and radiotherapy. Head Neck 2011, 33(2):251-256.
- [11]Mendelsohn AH, Lai CK, Shintaku IP, et al.: Histopathologic findings of HPV and p16 positive HNSCC. Laryngoscope 2010, 120(9):1788-1794.
- [12]Hafkamp HC, Speel EJ, Haesevoets A, et al.: A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5–8. Int J Cancer 2003, 107(3):394-400.
- [13]Chernock RD, El-Mofty SK, Thorstad WL, Parvin CA, Lewis JS Jr: HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol 2009, 3(3):186-194.
- [14]Wilczynski SP, Lin BT, Xie Y, Paz IB: Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma. Am J Pathol 1998, 152(1):145-156.
- [15]Laco J, Nekvindova J, Novakova V, et al.: Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) expression, and HPV status. Neoplasma 2012, 59(4):398-408.
- [16]Klimowicz AC, Bose P, Nakoneshny SC, et al.: Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma. Eur J Cancer 2012, 48(14):2166-2174.
- [17]Hong AM, Martin A, Armstrong BK, et al.: Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer. Ann Oncol 2013, 24(1):215-219.
- [18]Lewis JS Jr, Thorstad WL, Chernock RD, et al.: p16 Positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol 2010, 34(8):1088-1096.
- [19]Fakhry C, Westra WH, Li S, et al.: Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 2008, 100(4):261-269.
- [20]Oken MM, Creech RH, Tormey DC, et al.: Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol 1982, 5(6):649-655.
- [21]Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987, 40(5):373-383.