P53 Negative Group Research Articles

The Effectiveness of Tonsillectomy in the Diagnostic Workup of Squamous Cell Carcinoma Unknown Primary in the Head and Neck Based on p16 Immunohistochemistry

Background and Objectives: Despite the distinct entity of both p16-positive and p16-negative squamous cell carcinoma unknown primary in the head and neck (HNSCCUP), the diagnostic workup did not differ. The aim of the study was to determine the effectiveness of palatine tonsillectomy in the identification of primary tumours in two groups of p16-positive and p16-negative HNSCCUP. Materials and Methods: Patients with HNSCCUP managed in two tertiary care referral centres from 1 January 2014 to 31 December 2020 were analysed retrospectively. Results: Sixty-six patients with HNSCCUP diagnosis were included consecutively. HPV status of metastatic cervical lymph nodes using immunohistochemistry with p16 protein was available for all patients. The proportion of both p16-positive and p16-negative groups was not significantly different (p = 0.242). Of the 39 patients who underwent palatine tonsillectomy, tonsillar cancers were revealed histologically in 6 (15.4%) patients, and all these patients were p16-positive. No primary tonsillar tumour was found in the p16-negative group (0 of 17). The primary tumour identification rate in p16-positive HNSCCUP patients using palatine tonsillectomy was 27% (6 of 22). Conclusions: The diagnostic workup of HNSCCUP should be guided according to HPV/p16 status. Palatine tonsillectomy is a useful procedure in identifying primary cancer in p16-positive SCCUP patients, however, its effectiveness in p16-negative patients is debatable.

The Clinical Characteristics and Outcomes of Human Papillomavirus-Positive Nasopharyngeal Carcinoma in a Single-Institution Cohort.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer more frequent among East Asian populations compared with Western populations. While much is known about human papillomavirus's (HPV's) role in oropharyngeal cancer (OPC), little is known about its prevalence and prognostic value in NPC. The aim of this study is to investigate the role of HPV in NPC treated with definitive radiotherapy at a single institution. A retrospective cohort analysis of patient's medical records and HPV status treated for NPC in Rambam Health Care Campus (Rambam HCC). Immunohistochemical staining for p16 was used as a surrogate marker of HPV infection in the tumor cells. All specimens were stained and evaluated by pathologists at the referring center independently. In total, 87 patients diagnosed with NPC were treated at Rambam HCC between 2005 and 2018. Seventy-four patients had accessible data on the disease's clinical parameters and p16 status. In total, 10/74 (13.5%) had p16-positive staining in tumor cells; 75% were men and over 50% were smokers. The average age of diagnosis for the whole cohort was 48 years, being lower for p16-positive patients compared with p16-negative patients at 43 and 49 years old, respectively. A total of 84% of the patients had advanced disease of stage III and IV at presentation. Only 16% were diagnosed with stage I and II. Unlike the p16-negative group, the p16-positive group did not include any stage I or II disease. In univariate and multivariate analysis of overall survival rates, the age at diagnosis and the nodal spread status were the only statistically significant measures. P16 status was not found to be associated with survival. The HPV prevalence in NPC is nontrivial. p16-positive patients had significantly less nodal spread and tended to be younger. Both age and nodal status were significantly correlated with the survival, but P16 status was not prognostic. Further large-scale trials are needed to elucidate the role of HPV in NPC.

Impact of P16 Positivity on Clinical Outcomes in Nasopharyngeal Carcinoma: A Single Institution Study.

Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. It is prevalent in East and Southeast Asia and rare in non-endemic countries like the USA. P16 is a tumor suppressor gene and there are limited studies with inconsistent results describing the association of its positivity in immunohistochemistry and clinical outcomes. In this retrospective study, we compared progression-free survival (PFS) and overall survival (OS) based on p16 positivity in 60 patients with NPC. Materials and methods Patients aged above 18 years and followed between July 2015 and December 2020 were included in the study. P16 positivity was based on the immunohistochemistry of the biopsy sample. We compared PFS and OS among all p16-positive and negative patients, and then among patients with advanced disease (stage III or IV), and between p16-positive, negative, and unknown status patients. Results There were 15 p16-positive, and 28 p16-negative, with a median age of 54.3 years and 55.7 years respectively. Most patients in both groups were male, Caucasian, and had advanced disease (stage III or stage IV). Both median PFS (p=0.838) and OS (p=0.776) were 84 months in the p16-negative group but were not reached during the study period in the p16-positive group. Among advanced-stage patients, the PFS (p=0.873), and OS (p=0.773) of both groups were not statistically significant. P16 status was unknown for 17 patients, and PFS (p=0.785) and OS (p=0.901), when compared among patients with p16-positive, negative, and unknown status, were also statistically non-significant. Discussion and conclusion Our analysis suggests that p16 status does not predict clinical outcomes in NPC patients. Our sample size was limited but is larger than most studies describing this association. With different studies in the literature reporting disparate findings, we recommend larger prospective studies to better illustrate the impact of p16 positivity on clinical outcomes in NPC.

High-Grade Endometrial Stromal Sarcomas With YWHAE::NUTM2 Gene Fusion Exhibit Recurrent CDKN2A Alterations and Absence of p16 Staining is a Poor Prognostic Marker

High-grade endometrial stromal sarcomas (HGESSs) are aggressive uterine tumors harboring oncogenic fusion proteins. We performed a molecular study of 36 HGESSs with YWHAE::NUTM2 gene fusion, assessing co-occurring genetic events, and showed that these tumors frequently harbor recurrent events involving the CDKN2A locus on chromosome 9p. Using array-based copy number profiling and CDKN2A fluorescence in situ hybridization, we identified homozygous and hemizygous deletions of CDKN2A in 18% and 14% of tumors (n = 22 analyzed), respectively. While all YWHAE-rearranged HGESSs with retained disomy for CDKN2A were immunohistochemically positive for p16INK4 (p16), all tumors with homozygous deletion of CDKN2A showed complete absence of p16 staining. Of the 2 tumors with a hemizygous deletion of CDKN2A, 1 showed diffuse and strong p16 positivity, whereas the other showed complete absence of staining. In the p16-negative case, we did not find intragenic mutations or DNA promoter methylation to explain the p16 protein loss, implicating other mechanisms in the regulation of protein expression. In our cohort, subclonal or complete absence of p16 staining was associated with worse overall survival compared with positive p16 staining (1-year overall survival: 28.6% vs 90.7%, respectively; n = 32; P < .001), with all 7 patients in the p16-negative group having succumbed to their disease within 2 years of diagnosis. Our results suggested CDKN2A alterations as a cooperative driver of tumorigenesis in a subset of HGESSs with the YWHAE::NUTM2 gene fusion and showed p16 to be a potential prognostic marker.

The Survival of Patients with Triple Negative Breast Cancer Undergoing Chemotherapy Along with Lifestyle Change Interventions

Background: The survival of patients with triple-negative breast cancer subtype undergoing chemotherapy along with weight management, physical activity, and diet was examined. In addition, the relationship between the Overall Survival (OS) of patients with expression P53 and Ki 67 was investigated. Methods: The study was conducted on 110 patients admitted to oncology clinics between October 2009 and July 2018. The patients underwent five chemotherapy cycles, including Docetaxel, Epirubicin, and Cyclophosphamide once every 21 days followed by two cycles of Epirubicin, Cyclophosphamide, and 5-Fluorouracil. The patients also received guidelines for physical exercise, diet, and lifestyle change. Results: The median and mean follow-ups were 52.3 and 45.6 months respectively. Eight patients were metastatic and 103 were under adjuvant therapy, 13 of whom had relapses. The median relapse-free survival and mean OS were 44.4 months and 49.2 months respectively. OS for P53-negative patients was 64.2 months, eight patients relapsed in the P53-positive group, and two relapsed in the P53-negative group. Survival was more favorable in the negative group (P=0.021). The mean DFS in the P53- negative group was 96.1% and 76.3% in the P53-positive group, suggesting a more favorable status in the P53-negative group. Out of 110 patients, 20 died and 90 are still alive. Conclusion: Combining physical exercise, diet, and lifestyle change with chemotherapy increases the chance of a better response to treatment and a reduction in the rate of relapse during the first three years. The survival rate was better in p53-negative patients.

Expression of Ki67 and p53 and their Relationship with the Survival Time of High-Dose Hypofractionated Radiotherapy in Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> To analyze the expression of Ki67 and p53 in pancreatic cancer and their relationship with the survival time of high-dose hypofractionated radiotherapy. <h3>Materials/Methods</h3> The biopsies of 55 patients with pancreatic cancer were collected retrospectively before receiving high-dose hypofractionated radiotherapy. Immunohistochemical SP method was used to detect the expression of Ki67 and p53 in pancreatic cancer. Log-rank test was used to compare the difference of survival time between different expression levels. Cox model was analyzed by multivariate analysis. <h3>Results</h3> The expression rates of Ki67 and p53 protein in puncture tissues were 41.8% and 47.3%, respectively. Univariate survival analysis showed that the survival time of Ki67 and p53 negative expression group was significantly longer than that of positive group (P < 0.05). Multivariate analysis showed that Ki67, p53 and distant metastasis were independent prognostic factors of pancreatic cancer patients receiving high-dose hypofractionated radiotherapy. <h3>Conclusion</h3> The expression level of Ki67 and p53 protein in pathological tissue before treatment is an important index to predict the survival time of high-dose hypofractionated radiotherapy for pancreatic cancer.

Integrated analysis of lncRNA-associated ceRNA network in p16-positive and p16-negative head and neck squamous cell carcinoma.

Determination of human papillomavirus (HPV) status has become clinically relevant for head and neck squamous cell carcinoma (HNSCC) patients. p16 immunohistochemistry is one of the recommended methods for classifying HPV status. However, long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks linked to different p16-status HNSCC are still absent.In the present study, The Cancer Genome Atlas database provided RNA profiles as well as clinical information from 26 p16-positive HNSCC samples, 71 p16-negative HNSCC samples, and 44 adjacent normal control samples. Differentially expressed RNAs (DERNAs) between HNSCC samples and normal samples were identified by limma package in R. Functional enrichment analysis of differentially expressed mRNAs was performed using Clusterprofiler package in R. Survival analysis of DERNAs was carried out by survival package in R. The ceRNA network was constructed using GDCRNATools package in R.A total of 102 lncRNAs, 196 microRNAs (miRNAs), and 2282 mRNAs were identified as p16-positive-specific DERNAs. There were 90 lncRNAs, 153 miRNAs, and 2038 mRNAs were identified as p16-negative-specific DERNAs. Functional enrichment analysis revealed that the differentially expressed mRNAs in the p16-positive and the p16-negative group were mainly enriched in the “DNA replication” and “extracellular matrix -receptor interaction” pathway, respectively. Among the top 25 DERNAs, there were 1 key lncRNA, 1 key miRNA, and 1 key messenger RNA in the p16-positive group and 2 key lncRNAs, 1 key miRNA, and 2 key mRNAs in the p16-negative group were significantly related to the overall survival. Then the ceRNA network in the p16-positive and p16-negative group was constructed. There were 5 lncRNAs, 16 miRNAs, and 66 mRNAs included in the p16-positive group ceRNA network and 1 lncRNA, 4 miRNAs, and 28 mRNAs included in the p16-negative group ceRNA network. Among the RNAs in the ceRNA network, 5 mRNAs were significantly related to the overall survival.Taken together, we revealed the differential RNA expression profiling and the differential ceRNA network in the p16-positive and p16-negative group of HNSCC. Our findings provided a novel insight into this HPV-related cancer and potential biomarkers and therapeutic targets for HNSCC based on p16 status.

Ki-67 and p53 expression in head and neck mucosal melanoma: A clinicopathologic analysis of predictors of outcome

ObjectiveTo explore the prognostic value of Ki-67 and p53 in patients with head and neck mucosal melanoma by analyzing the relevant data from previous patients. MethodsData on Ki-67 and p53 immunohistochemical staining in 128 patients treated in Beijing Tongren Hospital between April 2005 and January 2021 were analyzed retrospectively. The correlation of Ki-67 and p53 expression with general clinical features and survival prognosis was analyzed. ResultsMedian follow-up time was 21 months. There were 66 cases in the group with Ki-67 < 40% and 62 cases in the group with Ki-67 ≥ 40%, with 60 cases in the p53-negative group and 68 cases in the p53-positive group. Of the 128 patients, 67 died and 61 survived. There were 63 patients with distant metastasis and 33 patients with local recurrence. Ki-67 expression was related to distant metastasis but this was not an independent risk factor; however, it was an independent risk factor affecting the survival of patients. The survival time for patients with Ki-67 ≥ 40% was significantly shorter than for patients with Ki-67 < 40%. P53 expression had no significant effect on survival and prognosis. ConclusionKi-67 is related to the disease stage and overall survival of patients with head and neck mucosal melanoma. It may have a guiding significance for the prognosis of patients as those with higher Ki-67 levels had poorer prognosis. However, the incidence rate of this disease is low, and all of the results need to be verified with a larger dataset.

Correlation of p16 immunohistochemistry with clinical and epidemiological features in oropharyngeal squamous-cell carcinoma.

BackgroundOropharyngeal cancer is an important public health problem. The aim of our study was to correlatep16 immunohistochemistry in oropharynx squamous cell carcinomas(OPSCC) with clinical and epidemiological features.Material and methodsWe conducted across-sectional study on patients with OPSCC treated at a single institution from 2014 to 2019. Epidemiological and clinical-pathological data were collected from medical records and a questionnaire was applied to determine alcohol consumption, smoking, and sexual behavior. The HPV status was determined by p16 immunohistochemistry.ResultsA total of 252 patients participated in the study, of these 221 (87.7%) were male. There were 81 (32.14%) p16 positive cases and 171 (67.85%) p16 negative cases. The p16positive group was significantly associated with younger patients (50–59 years), higher education level, lower clinical stage and patients who never drank or smoked. Through univariate logistic regression, we observed that female sex (OR, 3.47; 95% CI, 1.60–7.51) and higher education level (OR, 9.39; 95% CI, 2, 81–31,38) were significantly more likely to be p16 positive. Early clinical stage (AJCC8ed) was more associated with p16 positivity both in univariate (OR, 0.14; 95% CI, 0.07–0.26, p<0.001) and multivariate analysis (OR, 0.18; 95% CI, 0.06–0.49, p = 0.001).ConclusionThis study showed that drinkers and current smokers were less likely to be p16+. Female sex, higher education level and younger age at diagnosis were associated with a higher probability of being p16+. Additionally, there was a higher proportion of patients with early clinical stage (I or II) in the p16 positive group when compared to the p16 negative group.

Analysis of factors affecting the prognosis of patients with cervical intraepithelial neoplasia 2.

According to the 2014 World Health Organization Classification of Tumors of Female Reproductive Organs, patients with cervical intraepithelial neoplasia 2 (CIN2) have an equivocal diagnosis, but p16 is considered as the reference index for CIN2. Positive p16 expression in CIN2 is associated with high-grade squamous intraepithelial lesions (HSIL), whereas p16 negative lesions are low-grade squamous intraepithelial lesions. The purpose of the present study was to examine the clinical value of p16 and human papillomavirus (HPV) E6/E7 mRNA in the prognostication of patients with CIN2. From January 2013 to January 2016, 108 patients were diagnosed with CIN2 by biopsy and followed up at 6-month intervals at Peking University People's Hospital (Beijing, China). The expression of HPV E6/E7 mRNA was detected by in situ hybridization, while the expression of p16 and Ki-67 proteins was detected by immunohistochemistry. Of the 108 CIN2 cases, 20 progressed to HSIL/CIN3, 36 cases demonstrated persistence with CIN2 after the follow-up and 52 cases achieved regression (≤CIN1). Of the p16-positive 82 cases, 20 cases were detected to have progressed, whereas in the p16-negative group, no progression was observed. There were statistically significant differences among the p16-positive and negative groups (P<0.05). In the HPV E6/E7 mRNA-positive 69 cases, 18 cases were detected to have progressed, whereas in the HPV E6/E7 mRNA-negative 39 cases, progression was detected in only 2 cases. There were statistically significant differences among the HPV E6/E7 mRNA-positive and negative groups (P<0.05). The area under the receiver operating characteristics curve was plotted; the area under the curve for HPV E6/E7 mRNA was 0.745, that for p16 was 0.546 and that for Ki-67 was 0.501. The detection of HPV E6/E7 mRNA may provide important predictive information for the prognosis of CIN2, however p16 and Ki-67 proteins may provide little value.

P53 and Survival Rate in Penile Cancer.

BACKGROUND:Penile cancer accounts for 0.4-0.6% of all malignancy in men in Europe and the United States of America. It also accounts for 10% of all malignancy in men in some Asian, South American, and African countries. P53 protein has the function to regulate apoptosis in the cell cycle. Therefore, the presence of p53 in cells may indicate higher proliferative activity of the cells as a feedback mechanism, indicating disease progression.AIM:This study aims to identify the association between p53 expression and survival rate in penile cancer patients.METHODS:This study was a retrospective observational analytic study. This study was conducted in Pathology Anatomy Laboratory Faculty of the Medicine University of Sumatera Utara/Haji Adam Malik Hospital/University of Sumatera Utara Hospital to assess p53 expression. This study was conducted from January 2018 to December 2018.RESULTS:The total subjects in this study were 33 with the mean age of 50.79 ± 10.62. Based on clinical stage, patients in this study are divided into 11 patients (33.3%) in stage T II and 22 patients (66.7%) in stage T III/T IV. P53 expression was positive in 13 patients (35.3%). There were 19 patients (57.6) alive and 14 patients (42.4%) deceased. Statistical analysis using chi-square showed that there was an association between p53 expression and mortality (p = 0.011). In the Kaplan-Meier Curve for 3-year overall survival based on p53 expression, the survival rate in 36 months in the p53 positive group is 18%, while in p53 negative group, the survival rate was 60%. The survival rate based on p53 status was significantly different (p = 0.025).CONCLUSION:There is a significant association between p53 expression and mortality in penile cancer patients. In conclusion, p53 expression in penile cancer cells examined by immunohistochemistry may show prognostic values in the disease progression.

P53-positive expression in dysplastic surgical margins is a predictor of tumor recurrence in patients with early oral squamous cell carcinoma.

PurposeThis was a retrospective analysis of the impact of the expression of p53 in the dys-plastic surgical margins of early oral squamous cell carcinoma (OSCC) (pT1-2, N0).Patients and methodsSeventy-two patients with early oral squamous cell carcinoma (OSCC) were recruited. Margin characteristics were abstracted from the pathology report. Expression of p53 in dysplastic surgical margins was examined with the immunohistochemical method and was correlated with clinicopathological parameters and clinical outcomes.ResultsPatients with moderate/severe dysplasia had poor local relapse-free survival (RFS) compared to those with mild dysplasia. Thirty-two (44.4%) had at least one p53-positive margin, and there was a significant association between the expression of p53 and tumor recurrence (P<0.001). p53-positive expression was correlated with RFS in patients with dysplastic margins, and its expression in moderate/severe dysplastic groups had a worse RFS than mild dysplastic groups. We also found that the grade of the dysplasia margin was not correlated with RFS in p53-negative groups. Multivariable analysis validated p53 expression in dysplastic surgical margins as an independent risk factor for recurrence.ConclusionOur results validated that p53 expression was an independent risk factor for early OSCC with dysplastic surgical margins. Additional therapy and close follow-up are needed for these patients.

Relationship between the precursors of high grade serous ovarian cancer and patient characteristics: decreased incidence of the p53 signature in pregnant women.

ObjectiveTo investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy.MethodsWe prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol.ResultsOf the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity.ConclusionsThe incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.

P53, latent membrane protein 1, bcl-2, and prognosis in nasopharyngeal carcinoma: a meta-analysis.

The controversy of (p53) in nasopharyngeal carcinoma persists, despite the fact that many studies have been conducted on its correlation with latent membrane protein 1 (LMP1), bcl-2, and prognosis. To better understand this postulated relationship, a meta-analysis was performed based on existing relevant studies. A total of 19 individual studies with a total of 1189 patients were included in the meta-analysis. Overall, the results revealed a significant association of p53-positive status with a poor 5-year survival of nasopharyngeal carcinoma (NPC) patients as the risk difference (RD) was -0.17 (95% CI, -0.31, -0.03; P=0.02, Pheterogeneity =0.01).The overall odds ratio (OR) for LMP1 in the p53 positive group vs. negative group revealed that a significantly elevated risk of positive LMP1 in the former was achieved (OR 5.52 95% CI, 2.66-11.46; P<0.00001, Pheterogeneity =0.78). Similarly, a strong correlation between bcl-2 and p53 was found with an OR 6.85 (95% CI, 2.37-19.74; P=0.0004, Pheterogeneity =0.48). However, there did not appear to be any correlations with clinical parameters such as gender, tumor site, lymph node metastasis,pathological type and TNM stage. In conclusion, p53 expression is related to the survival of nasopharyngeal carcinoma. It can be considered as the auxiliary detection index in treatment and prognosis of nasopharyngeal carcinoma.

P16 positivity and regression grade predict survival after neoadjuvant radiotherapy of OSCC.

Survival after preoperative radiotherapy in locally advanced head and neck squamous cell cancer is associated with pathological response. The prognostic importance of p16 expression in these patients has not been established yet. Ninety-seven patients with oral squamous cell carcinoma, treated preoperatively with radiotherapy in combination with chemotherapy or cetuximab, were included in this retrospective analysis. Survival rates were estimated by the Kaplan-Meyer method. Pathological response was evaluated by histological analysis and p16 expression by immunohistochemistry. Overall survival after 2years was 66% for the entire group, 92% in the p16-positive and 62% in the p16-negative group, respectively. 12.4% of the tumours were p16-positive. P16 expression (HR 6.98, p=.05) and regression grade (HR 2.94, p=.001) had a statistically significant impact on prognosis. 83.3% of p16-expressing tumours were pathological responders. All p16-positive patients with pathological response were alive within the observation period. P16 expression is associated with prognosis in preoperatively irradiated OSCC patients. The association between p16 positivity, regression grade and improved survival provides a rationale for de-intensification strategies in patients with head and neck cancer who respond well to neoadjuvant therapy, a concept that is being tested in prospective clinical trials.

Do patients with p16-positive oropharyngeal squamous cell carcinoma get more bone metastasis than p16-negative patients?

Oropharyngeal squamous cell carcinoma is thought to rarely metastasise to bone. This study hypothesised that in p16-positive disease there is a significant incidence of bony metastasis. This was an ambispective cohort review. All patients with oropharyngeal squamous cell carcinoma diagnosed and treated at one centre were included. A total of 180 consecutive patients were identified over 5 years. Fifteen patients were excluded because of lack of p16 status, none of whom had bony metastasis. The final analysis included 165 patients: 48 (29.09 per cent) in the p16-negative group and 117 (70.91 per cent) in the p16-positive group. Ten patients (8.55 per cent) in the p16-positive group developed bony metastasis, compared with zero in the p16-negative group; this difference was statistically significant (p = 0.036). Expression of p16 was associated with an increased incidence in bony metastasis in this cohort. This is the first study to explore this specific question.

Relationship Between p16 Expression and Prognosis in Patients with Oropharyngeal Cancer Undergoing Surgery.

Prognostic impact of p16 expression in patients with oropharyngeal squamous cell carcinoma (OSCC) undergoing surgery is not fully examined. The aim of this study was to clarify these issues. Sixty-four OSCC subjects were analyzed. Immuno-histochemical staining of p16, a surrogate marker for human papillomavirus (HPV), was performed histopathologically. Data were retrospectively analyzed according to p16 positivity and factors linked to prognosis were also analyzed. No significant difference was observed in the prognosis between the p16-positive group (n=28) and the p16-negative group (n=36). In patients undergoing post-operative radiation, the p16-positive group (n=18) had a significantly better prognosis than the p16-negative group (n=6). On multivariate analysis, transoral surgery was a significant predictor of overall survival (p=0.0173). Prognostic impact of p16 can be emphasized in a subgroup of OSCC patients undergoing surgery. Surgery with sufficient surgical margin may be chosen as the first treatment for HPV-negative OSCC in some cases.

Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues.

BackgroundThis study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1.Methods PV‐9000 two‐step immunohistochemistry was used to analyze protein expression.ResultsThe positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para‐carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para‐carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05).Conclusion Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer.

Assessment of treatment response to immunotherapy in melanoma patients with pathogenic mutations of NRAS, BRAF, CDKN2A and P53.

e21057 Background: BRAF, NRAS, CDKN2A and P53 mutations are commonly observed pathogenic mutations in cutaneous melanoma. The influence of mutations such as BRAF, NRAS, CDKN2A and P53 on treatment response in the PD1 inhibitor era has not been well defined. Methods: This study included patients with melanoma with a cutaneous or unknown primary. All patients had genomic profiling with the Mayo Clinic 50-gene solid tumor mutation panel. Treatment response to first line immunotherapy with PD1, CTLA-4, or combination PD1/CTLA-4 inhibitors were assessed by response rate and time-to-progression (TTP) rate at 12 months. Each patient outcome was stratified by non-mutually exclusive gene mutation status into BRAF, NRAS, P53, CDKN2A, or quadruple negative (N4) groups. Results: Genomic profiling was performed on 208 patients, of whom 102 received first line immunotherapy. Most patients received a PD1 inhibitor (n = 62), followed by CTLA-4 inhibitor (n = 34), and combination therapy (n = 6). A trend towards improved outcomes was observed in CDKN2A and BRAF mutated patients with worse outcomes noted in P53, N4, and NRAS patients. The percent without progression at 12 months were BRAF 52.2%, CDKN2A 58.2%, NRAS 30.5%, P53 37.7%, and N4 26.7% (see table below). Response rates were BRAF 46.4%, CDKN2A 38.5%, NRAS 22.2%, P53 40.0%, and N4 33.3%. Conclusions: There is a trend towards improved outcomes with immunotherapy in BRAF and CDKN2A mutated patients while P53, NRAS and N4 patients have inferior outcomes. [Table: see text]

FGFR3 correlation with mutant p53 and its prognostic value in oropharyngeal squamous cell carcinoma (OPSCC).

6057 Background: Fibroblast growth factor receptor 3 (FGFR3) is expressed in squamous cell carcinoma of the head and neck (SCCHN) including oropharyngeal squamous cell carcinoma (OPSCC) and is a potential therapeutic target. Information on its prognostic value and its correlation with other relevant cancer related proteins is limited. Methods: We performed immunohistochemistry (IHC) analyses of p16, mutant p53 (mp53), and FGFR3 on 221 retrospectively collected OPSCC tissue samples. mp53, and FGFR3 were semi-quantified as weighted index [WI = % positive x intensity (0. 1+, 2+, and 3+)]. Correlations of FGFR3 WI with p16 status, and mp53 WI were analyzed. Association of FGFR3 with disease-free survival (DFS) or overall survival (OS) was assessed. Results: A total of 144/221 (65%) were p16 +, 93/172 (54%) had mp53, and 140/221 (63%) expressed FGFR3. FGFR3 was highly correlated with mp53 (p &lt; 0.001), which was true in both p16 + and – OPSCC (p &lt; 0.0001 and p = 0.0006, respectively).mp53 level was significantly lower in p16 positive versus p16 negative group (p &lt; 0.0001). Univariate analysis revealed an association of p16 negative and high mp53 with worse OS (p &lt; 0.001 and p &lt; 0.001, respectively) and DFS (p &lt; 0.001 and p = 0.004, respectively). FGFR3 was associated with worse OS and DFS (p = 0.014 and p = 0.047, respectively). On multivariable analysis FGFR3 was associated with worse DFS (p = 0.005), but not OS. Kaplan-Meier plot using medians of both FGFR3 and mp53 as the cut-off values showed that higher FGFR3 and mp53 correlated to worst DFS (p = 0.025) and OS (p = 0.009). Conclusions: Our results suggest that FGFR3 is associated with mp53 and p16 – OPSCC and correlates with worse clinical outcome. The biologic relation of FGFR3 and mp53 in OPSCC deserves further investigation. (This research was supported by a grant NCI R21 CA182661-01A1to NFS and GZC).