cyclin-d1 and HIV-Infections

Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC.. The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups.. HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53.. HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society.

Topics: Adult; Aged; Cadherins; Carcinoma, Squamous Cell; Case-Control Studies; Caspase 8; Class I Phosphatidylinositol 3-Kinases; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; ErbB Receptors; F-Box-WD Repeat-Containing Protein 7; Female; Head and Neck Neoplasms; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; HIV Infections; HLA-A Antigens; Humans; In Situ Hybridization; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; LIM Domain Proteins; Male; Middle Aged; NF-E2-Related Factor 2; Nuclear Proteins; Papillomaviridae; Papillomavirus Infections; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins p21(ras); Receptor, Notch1; Receptor, Notch2; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Squamous Cell Carcinoma of Head and Neck; Transcription Factors; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).. In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters.. Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19.. Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to higher-grade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

Topics: Adult; Aged; Aged, 80 and over; Autopsy; beta Catenin; Brazil; Carcinoma, Hepatocellular; Case-Control Studies; Caspase 3; Cross-Sectional Studies; Cyclin D1; ErbB Receptors; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; HIV Infections; Humans; Immunohistochemistry; Keratin-19; Ki-67 Antigen; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Proto-Oncogene Proteins c-met; Retrospective Studies; Tissue Array Analysis; TOR Serine-Threonine Kinases; Tumor Suppressor Protein p53; Vimentin

To determine whether changes in the indices of HIV-associated cell cycle dysregulation (i.e., increased expression of cyclin B1 and abnormal nucleolar structure) may predict the level of immunological reconstitution in HIV-infected patients treated with highly active antiretroviral therapy (HAART).. Cross-sectional and longitudinal analysis of viral load, CD4 T cell counts, cyclin B1 expression, and AgNOR number and area of distribution in 30 HIV-infected patients who were studied before and up to 6 months after initiation of HAART.. In HIV-infected individuals, the level of cell cycle dysregulation correlated with the type of response to HAART. While low levels of dysregulation were present in patients with complete (both virological and immunological) response to HAART, high levels were present in HAART-treated patients with limited CD4 T cell increases despite persistent viral suppression (immunological non-responders). Importantly, the level of correction of cell cycle dysregulation after 60 days of therapy predicted the level of immune reconstitution after 6 months.. These observations suggest that correction of cell cycle dysregulation predicts a good immunological response to HAART and that sequential analysis of cell cycle dysregulation might help to identify patients that could benefit from alternative, immune-based interventions in addition to standard HAART.

Topics: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cell Cycle; Cross-Sectional Studies; Cyclin B; Cyclin B1; Cyclin D1; HIV Infections; Humans; Longitudinal Studies; Nucleolus Organizer Region; Prognosis; Retinoblastoma Protein; Treatment Outcome; Viral Load