Abstract 2041: Lesion pathology and oral-cancer associated pain in the 4NQO oral carcinogenesis model

Abstract

Abstract Oral cancer is a painful and debilitating type of cancer. Oral cancer patients frequently experience severe pain while eating and talking. Pain is attributed to neuronal sensitization by the release of chemical mediators from the cancer cells and cancer microenvironment. Not all oral cancers are painful. Patients with painful oral cancers are more likely to have worse prognosis and metastatic disease, and their pain is not well managed with NSAIDs or opioid analgesics. Therefore, there is an unmet clinical need to identify the underlying mechanisms of oral cancer pain. This study was designed to identify pathological lesions associated with increased pain in a preclinical model of oral cancer and pain. Forty C57BL/6 female mice were treated with 4-nitroquinoline 1-oxide (4NQO) for 16 weeks, and followed for the development of tongue lesions for 12 weeks. Concurrently, change in nociceptive behavior (i.e., the animal equivalent of pain behavior) was measured using a validated operant assay and device for measuring functional mechanical allodynia (the dolognawmeter). Nociception (pain) scores and histopathological data were obtained from 36 animals. Mice developed a spectrum of tongue and esophageal lesions including hyperkeratoses, papillomas (exophytic lesions), dysplasias and cancers. Papillomas included lesions with benign and dysplastic pathological features, indicating that both lesion types were in the continuum of malignant transformation. Mice harbored lesions associated with low pain scores (n=9), intermediate pain scores (n=16) and high pain scores (n=11). Three pathological subsets of squamous cell carcinomas (SCCs) were identified that displayed stromal invasion (iSCC), deep stromal invasion >1.5mm depth (diSCC) and cancers with exophytic and invasive morphology associated with papillary lesions (pSCCs). Increased nociceptive behavior was associated with pSCCs in univariate and multivariate analyses. Cancers of the pSCC subtype are expected to be enriched for expression and release of nociceptive mediators. The study demonstrates that the 4NQO model recapitulates human cancer with respect to development of cancers differing in level of cancer associated nociception. Citation Format: Keyur Naik, Malvin N. Janal, Jason Chen, Daniel E. Bandary, Branden Brar, Aditi Bhattacharya. Lesion pathology and oral-cancer associated pain in the 4NQO oral carcinogenesis model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2041.