The effect of P53 expression and smoking/alcohol in P16(+) and P16(-) oropharyngeal carcinoma and risk classification: the Turkish Society of Radiation Oncology Head & Neck Study Group 01-002.

OBJECTIVE: The aim of this study is to categorize the risk groups of patients with oropharyngeal carcinoma (OPC) according to p16 and p53 status, smoking/alcohol consumption history, and other prognostic factors. STUDY DESIGN: The immunostaining of p16 and p53 of 290 patients was retrospectively evaluated. The history of smoking/alcohol consumption of each patient was noted. p16 and p53 staining patterns were reviewed. The results were compared with demographic findings and prognostic factors. Risk groups have been classified for the p16 status of patients. RESULTS: The median follow-up was 47 months (range 6-240). Five-year disease-free survival (DFS) rates for patients with p16 (+) and (-) were 76% and 36%, and overall survival rates were 83% vs 40%, respectively (HR = 0.34 [0.21-0.57], P < .0001), HR = 0.22 [0.12-0.40] P < .0001, respectively). p16(-), p53(+), heavy smoking/alcohol consumption, performance status; advanced T and N stages in patients with p16(-), and continuing smoking/alcohol consumption after treatment were found to be unfavorable risk factors. Five-year overall survival rates were 95%, 78%, and 36% for low, intermediate, and high-risk groups, respectively. CONCLUSIONS: The results of our study have shown that p16 negativity in patients with oropharyngeal cancer was found to be an important prognostic factor, especially for those with lower p53 expression and not smoking/consuming alcohol.

TMC8 mutation in a Turkish family with epidermodysplasia verruciformis including laryngeal papilloma and recurrent skin carcinoma.

The vast majority of primary immunodeficiencies (PIDs) occur due to the defects in cells originating from hematopoietic stem cells, while in some PIDs, there are defects in various genes responsible for non-leucocyte immune response such as seen in epidermodysplasia verruciformis (EV). EV caused by the mutations in TMC6, TMC8, and CIB1 genes is called "typical." "Atypical" EV may develop in patients with primary immunodeficiencies originating from hematopoietic stem cells, which include severe T-cell failure, caused by inactivating biallelic mutations of STK4, RHOH, CORO1A, ITK, TPP2, DCLRE1C, LCK, RASGRP1, or DOCK8 genes. Here, we present a family with TMC8 gene mutation leading to disseminated epidermodysplasia verruciformis including laryngeal papilloma and recurrent cutaneous squamous cell carcinomas. Typical EV with impaired local, keratinocyte-intrinsic immune response should be considered when routine immunological examinations are normal in patients presenting with clinical signs of EV. Although it is not possible to prevent EV lesions, early and appropriate surveillance for malignancy is mandatory.

Human papillomavirus infection in patients with laryngeal carcinoma.

BACKGROUND: The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol. METHODS: The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping. RESULTS: HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity. CONCLUSIONS: HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted.

Prevalence of Epidermal Growth Factor Receptor Mutations in Patients with Non-Small Cell Lung Cancer in Turkish Population.

AIMS: Epidermal growth factor receptor mutation analysis in non-small cell lung cancer is important for selecting patients who will receive treatment with tyrosine kinase inhibitors. In this study, we aimed to investigate the prevalence of epidermal growth factor receptor mutations and mutation patterns in the Turkish population. METHODS: We retrospectively reviewed molecular pathology reports of 959 cases with lung cancer analysed for epidermal growth factor receptor mutations. We analysed all four epidermal growth factor receptor exon mutations using a real-time polymerase chain reaction platform. RESULTS: In this study, the epidermal growth factor receptor mutation rate in the Turkish population was 16.7% (160 of 959). The epidermal growth factor receptor mutation frequency was significantly higher in women (37.1%, n=96) than in men (9.1%, n=64) (p<0.001). In addition, the epidermal growth factor receptor mutation rate was higher in the adenocarcinoma histologic type (p<0.001). Patients with mutations were older than those without mutations (p=0.003). The most frequent mutations were exon 19 deletions (48.8%, 78/160) and exon 21 L858R point mutations (38.1.1%, 61/160). We also detected compound mutation patterns in three cases (1.9%). CONCLUSION: The prevalence of epidermal growth factor receptor mutations in the Turkish population was slightly higher than that in the Caucasian population and lower than that in the East Asian population. The results of this study may provide guidance in personalized therapy of non-small cell lung cancer in the Turkish population.

Comparison of Clinicopathologic Parameters and Survivals Between Epstein-Barr Virus-positive and Her2-positive Gastric Cancers.

Gastric carcinomas are highly mortal neoplasms for which new therapeutic options are being searched. The molecular subtyping of gastric adenocarcinomas was proposed recently, and the relationship between etiopathogenetic types is still under investigation. Here we compared histopathologic, prognostic, and survival differences between Epstein-Barr virus (EBV)-positive and Her2-positive gastric adenocarcinomas. In a retrospective design, we searched the EBV status with Epstein Barr Virus encoded small RNA (EBER) in situ hybridization, and the Her2 status both by immunohistochemistry and by chromogenic in situ hybridization of 106 gastrectomized gastric carcinomas. Histologic and clinical prognostic parameters and survival information were determined, and retrieved from archival tissues and clinical notes. The Her2 positivity rate was 12.3% and the EBV positivity rate was 7.6%. Among EBER-positive cases, Her2 positivity was not detected. Her2 positivity was detected more in intestinal differentiated tumors, whereas EBER positivity was detected in undifferentiated tumors (P=0.003). There was no correlation of Her2 or EBER positivity with the tumor stage. Median survivals of EBER-positive, Her2-positive, and both negative cases were 11.5, 18, and 20.5 months, respectively. The tumor stage and distant metastasis were found to be significant for survival in the multivariate analysis. In our 106 gastrectomized gastric carcinoma cases, EBV-positive and Her2-positive groups were found to be unrelated as proposed in the upcoming classification of gastric carcinomas.

Retrospective analysis of oncogenic human papilloma virus and Epstein-Barr virus prevalence in Turkish nasopharyngeal cancer patients.

Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV). Human papilloma virus (HPV) has also been detected in NPC cases. In this retrospective study, we analyze the frequency of EBV and HPV infection in 82 Turkish patients with NPC. A total of 82 were evaluated for EBV and HPV. In situ hybridization (ISH) was performed for EBV. HPV-ISH and P16 immunohistochemistry used to determine the HPV status. Seventy-two of the 82 (87%) NPC patients were EBV-positive. The highest rate of EBV-positivity was found in undifferentiated NPC patients, which accounted for 65 of 68 (95.6%) undifferentiated cases. One of the 82 NPC patients whose tumor was non-keratinizing differentiated, contained HPV. Our data shows that EBV is closely associated with NPC in Turkey. We found lower rates of HPV-positivity in NPC patients than in North American populations. In addition, both EBV and HPV-negativity were more associated with decreased survival than EBV-positive cases.

Occurrence of dysplasia and human papilloma virus typing in penile condylomas.

OBJECTIVE: To determine the incidence of dysplasia as a preneoplastic change and high-risk human papilloma virus (HPV) infection in penile condylomas, which are common HPV-related lesions and considered a risk factor for penile cancer. METHODS: Histologic analysis was done of 58 consecutive penile condylomas with tissue diagnosis. An immunohistochemical panel that included stains for p53, Ki-67, and p16INK4a was also used. HPV typing was successfully performed in 43 lesions. Genotyping was accomplished through polymerase chain reaction and flow-through hybridization with an HPV GenoArray Diagnostic Test kit. RESULTS: Dysplasia was observed in 13 of the 58 condylomas (22%). High-risk HPV DNA was detected in 5 of 10 dysplastic lesions (50%) for which tissue blocks were available for study. High-risk HPV was not detected in the nondysplastic lesions (P<.001). Ki-67≥20% above the basal layer of epithelium and p53-positive immunostaining occurred more frequently in dysplastic lesions than in nondysplastic lesions; however, the difference was not statistically significance. Staining for p16INK4a was not helpful. CONCLUSION: Anogenital condylomas in men are usually treated using destructive methods or with medication. We suggest that at least a part of the lesion must be removed and sent for histopathologic examination. If the histologic result shows significant dysplastic alteration, the lesion should be further investigated to determine the subtype of infective virus, because 50% of such lesions are associated with high-risk HPV. When oncogenic pathogens are found, careful patient follow-up for recurrences and counseling for the patient and his sexual partner(s) may be warranted.