Evaluation of prognostic markers for oropharyngeal carcinoma using tissue microarray

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing in many Western countries. In Finland, the incidence increased from 32 cases in 1996 to 85 cases in 2006 to 193 cases in 2016. Globally, OPSCC is the 12th most common cancer and is frequently related to human papillomavirus (HPV) infection. The prediction of OPSCC prognosis is one of the main dilemmas for the clinicians. Although many parameters have been used to predict the prognosis, such as clinical factors of tumor size and invasion, lymph node and distant metastases (cTNM) staging, and other prognostic models based on histopathologic parameters; in addition to the patient-related and treatment-related factors, all of these parameters are of limited value in predicting prognosis. For this reason, assessing of the immunohistochemical markers as prognostic biomarkers was a target for many recent studies. Tolllike receptors (TLRs) play important roles in the development of carcinoma of different sites including the tongue, cutaneous, cervical and laryngeal squamous cell carcinoma, and colorectal adenocarcinoma. Hormone receptors play a crucial role in the pathogenesis and treatment of breast carcinoma and carcinoma of the male and female genital organs, in addition to their role in carcinomas of other organs including stomach, larynx, and salivary gland, but their role in OPSCC still poorly understood. During the epithelial to mesenchymal transition (EMT), the epithelial cells lose some of their essential epithelial characteristics and gain invasive and migratory characteristics, which are properties of the mesenchymal cells. In addition, HPV infection induces keratinocyte stem cells to behave like cancer stem cell (CSCs). Detection of more specific prognostic biomarkers would be beneficial on the clinical level. In this thesis project, we examined the prognostic value of TLR5, 7 and 9, sex hormone receptors: androgen receptors (AR), progesterone receptors (PR), and estrogen receptors (ER), EMT markers: β-catenin, E-cadherin, vimentin, and biomarkers expressed by stem cells: Bmi-1, HESC5:3, and HES77 in a cohort of 202 OPSCC patients. We also examined the correlations of these markers with HPV infection. We found that high TLR5, low TLR7, and high PR levels are associated with poor disease-specific survival (DSS) (p=0.002 and p=0.001 respectively). In addition, HPV-positive OPSCCs express higher levels of TLR7 (p<0.001), AR (p<0.001), HESC5:3 (p=0.016), vimentin (p=0.026), and cell membranous β-catenin (p=0.001), and lower levels of TLR5 (p<0.001), TLR9 (p<0.001), PR (p<0.001), and Bmi-1 (p=0.006) than the HPV-negative OPSCCs. From our findings, we conclude that high TLR5, low TLR7, and high PR expression levels may impact the prognosis of OPSCC. In addition, our results support the fact that HPV-positive and HPV-negative OPSCCs are different tumor entities.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2019

Author dc:creator

• Mohamed, Hesham E. Abdolhfid

• Pathology, Cancer, Immunohistochemistry.

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
• This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
• Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/304892

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F304892