HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy

Control of the mitotic exit network during meiosis

The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find that the signaling pathway is active only during meiosis II. Our analysis further shows that MEN signaling is modulated during meiosis in several key ways. Whereas binding of MEN components to spindle pole bodies (SPBs) is necessary for MEN signaling during mitosis, during meiosis MEN signaling occurs off SPBs and does not require the SPB recruitment factor Nud1. Furthermore, unlike during mitosis, MEN signaling is controlled through the regulated interaction between the MEN kinase Dbf20 and its activating subunit Mob1. Our data lead to the conclusion that a pathway essential for vegetative growth is largely dispensable for the specialized meiotic divisions and provide insights into how cell cycle regulatory pathways are modulated to accommodate different modes of cell division.National Institutes of Health (U.S.) (Grant number GM62207)Howard Hughes Medical Institute. Investigato

Comorbidity prior to diagnosis in patients with common cancer diagnoses

e22180 Background: Chronic disease as diabetes, hypertonia and anemia may be associated with cancer risk as well as affect the short term survival of the malignancy. Methods: Using population based registry data from specialist and primary care in our health care region comorbidity in the form of anemia, hypertonia, diabetes, rheumatoid arthritis, chronic obstructive pulmonary diasease (KOL), and alcohol related diseases for patients with colon-, rectal-, lung-, prostate and breast cancer and survival were studied. Altogether 2047 colon cancer cases, 985 rectal cancer cases, 2017 lung cancer cases, 3578 breast cancer cases and 5106 prostate cancer cases diagnosed 2000–2005 were included. Results: were age and sex adjusted and one year survival was calculated. Comorbidity was studied prior to cancer diagnosis and in order to compare with the general population all first comorbidity diagnoses within 90 days were censored. Results The prevalence of the chronic diseases in the general population was for all ages diabetes 3.2%, rheumatoid arthritis 0.5%, hypertonia 6.8%, anemia 1.1%, KOL 1.0% and alcohol related diagnoses 0.7%. Patients with colon and rectal cancer had a higher prevalence of anemia, and diabetes. Patients with lung cancer had a higher prevalence of anemia, KOL, diabetes, rheumatoid arthritis for both men and women and for men also a higher prevalence of alcohol related diseases. Except for alcohol related diseases in females with breast cancer comorbidity for the above diseases was not significantly elevated for breast or prostate cancer. For all diagnoses hypertonia was significantly lower than in the general population. Survival of the different cancer diagnoses was not significantly related to the comorbidity except for a tendency of worse survival for patients with alcohol related disease. Conclusions: The prevalence of some common chronic diseases are elevated especially in colon-, rectal and lung cancer patients. The comorbidity does not seem to affect short term survival of the cancer patient except for alcohol related diagnoses. Our study also indicates the necessity to have all levels of care included in the study base of comorbidity and also emphasizes the need to censor time prior to diagnosis when comparing data with the general population. No significant financial relationships to disclose. </jats:p

P1-08-06: Breast Cancer among Patients with Diabetes, Obesity and Abnormal Blood Lipids – A Population-Based Register Study in Sweden.

Abstract Objective: To study how the incidence of breast cancer is related to diabetes, obesity or abnormal blood lipids. Methods: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0–10 years prior to the diagnosis of cancer in 2724 cases of cancer and in 20542 controls matched regarding age, sex and domicile in a population based material. Diagnoses were obtained by using out and inpatient population based registries. Also the use of glargine and metformin was studied in relation to cancer risk in diabetic patients using the national pharmacy prescription registry. Conditional logistic regression was used for the analyses. Results: Diabetes was significantly more common prior to diagnosis in patients with breast cancer with diabetes diagnosed 0–4 years prior to the cancer diagnosis. The findings remained after adjusting for obesity and high blood lipids. Obesity was significantly more common in patients with breast cancer above the age of 60 years in those where obesity was diagnosed close to the diagnosis of cancer. High blood lipids were significantly less common in patients with breast cancer close to diagnosis. Glargine use was associated with a doubled risk 2.88 (1.15−6.64) and metformin use with a lower risk of cancer in diabetic patients 0.92 (0.82−1.09). Conclusions: Within 4 years of diagnosis diabetes, obesity after age 60 and low blood lipids are associated with breast cancer. Glargine use seems to increase overall cancer risk. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-06.</jats:p