A high Pol expression was observed in the germinal centers, which is consistent with previous studies and its role in somatic hypermutation in germinal center [45-47]. (Duarte, CA) were retrospectively analyzed. Pretreatment samples were immunostained with anti-Pol antibody and the correlation between the expression level of Pol and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40) or gemcitabine (n=9) based chemotherapy were further examined for Pol expression Rabbit Polyclonal to RPL39 level for comparison with patient response to chemotherapy. Results The expression of Pol was elevated in 67% of the head and neck tumor samples. Pol expression level was significantly higher in grade 1 to grade 2 tumors (well to moderately differentiated). The overall benefit rate YYA-021 (complete response+ partial response) in patients treated with platinum and gemcitabine based chemotherapy was 79.5%, where low Pol level was significantly associated with high complete response rate (p=0.03), although not associated with overall survival. Furthermore, no significant correlation was observed between Pol expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status. Conclusions Our data suggest that Pol expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy YYA-021 for HNSCC. Introduction Mucosal derived squamous cell carcinoma of the head and neck (HNSCC) refers to a group of biologically similar cancers originated from the mucosal squamous epithelial lining of upper aerodigestive tract, including the lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, and larynx. HNSCC is the sixth most frequently occurring cancer worldwide and accounts for 2% of all cancer death annually. According to the American Cancer Society, 36,540 Americans were diagnosed with head and neck cancer in 2011 and 7,880 died from the disease [1,2]. Most patients present lymph node metastatic disease at the time of diagnosis, and the five-year survival rate of those patients is around 35% ; which YYA-021 has not improved over the last decade . Platinum-based combination regimen, such as cisplatin/oxaliplatin plus 5-FU and taxotere, is the current first-line neoadjuvant chemotherapy for locally advanced HNSCC . However, the poor or partial response to platinum-based chemotherapy of HNSCC remains an enigma for oncologists. Platinum compounds form DNA intrastrand or interstrand cross-links that severely block DNA synthesis and result in mutations and apoptosis . These platinum induced adducts are repaired by nucleotide excision repair system (NER) [6,7], the mismatch repair (MMR) system, and recombination repair (RR) . In addition, DNA translesion synthesis (TLS) polymerases have also been shown to have the ability to bypass cisplatin-induced intrastrand adducts [9,11,39,40]. This suggests these bypass polymerases provide an alternate mechanism in handling platinum compound induced DNA adducts and may contribute to the observed resistance against these compounds [9,11]. Among the TLS DNA polymerases, DNA Polymerase (Pol ; hRad30a gene; xeroderma pigmentosum variant gene product) is the only one with well-understood biological function, which is usually to replicate across the cis-syn cyclobutane pyrimidine dimers (CPDs) that induced by UV YYA-021 radiation . Genetic defects in the gene encoding Pol results in Xeroderma Pigmentosum Variant (XP-V) disease, and XP-V patients are highly sensitive to UV irradiation and prone to the development of skin cancer . Pol has also been shown to have the ability to bypass a broad range of DNA lesions, such as 7,8-dihydro-8-oxoguanine , (+]-trans-anti-benzopyrene-N2-dG , acetylaminofluorene-adducted guanine , O6-methylguanine , and thymine glycol . In addition, it has been exhibited that Pol can modulate the cellular sensitivity to chemotherapeutic brokers . The Pol deficient cells derived from XP-V patients were more sensitive to -D-arabinofuranosylcytosine (cytarabine, araC), gemcitabine, and cisplatin . Cellular and biochemical analyses suggested that the higher sensitivity of XP-V cells to these brokers is due to the lack of Pol activity in facilitating the resumption of the paused DNA replication caused by therapeutic brokers [13,14]. Pol bypasses the Pt-GG intrastrand crosslinked adducts with a relative higher efficiency and fidelity, as comparing to other TLS enzymes [42-44]. Studies have also exhibited that the expression level of Pol negatively correlated with cisplatin sensitivity of non-small cell lung cancer (NSCLC) cell lines . Furthermore, Pol protein expression was suggested to be an independent predictive marker for the treatment response and survival of metastatic gastric adenocarcinoma YYA-021 patients who are treated with oxaliplatin-based chemotherapy . In this study, we examined the associations between expression of Pol proteins and known prognostic factors including staging and tumor differentiation. We also examined the associations between expression of Pol proteins and response to platinum or gemcitabine based chemotherapy treatment and survival in HNSCC. Materials and Methods Patient characteristics Tumor blocks for sixty-four patients diagnosed with mucosal derived squamous cell carcinomas of head and neck (HNSCC) from 1989 and 2007 at the City of Hope National Medical Center (Duarte, CA) were retrospectively analyzed. Tumor blocks included tumors of the nasopharynx, paranasal sinuses, oral cavity, oropharynx,.