Association between oropharyngeal cancers with known HPV and p16 status and cervical intraepithelial neoplasia: a Danish population-based study.

BACKGROUND: Persistent infection with high-risk genotypes of human papillomavirus (HPV) is the main risk factor in the development of uterine cervical precancerous lesions and cervical cancer (CC), and cases of HPV-induced oropharyngeal squamous cell carcinoma (OPSCC) is increasing in the Western world. We investigated the association between HPV and p16 status and previous results of cervical examinations, including cytological and histological tests, in females with OPSCC. MATERIAL AND METHODS: We included females diagnosed with an OPSCC in Eastern Denmark from 2000 to 2014. OPSCCs were assessed for p16-overexpression and HPV DNA PCR. History of cervical tests was obtained from the Danish Pathology Registry. The cytology and histological results were categorized in accordance with the 2014 Bethesda System (TBS) and WHO. Hence, we divide the cervical results into two groups. Group I were negative for intraepithelial lesion or malignancy and group II had epithelial cell abnormalities and subdivided after increasingly neoplastic severity from A-D. Chi2-tests and Fischer's exact tests were performed to compare the two groups. RESULTS: A total of 417 women with OPSCC were identified; 203 with HPV-positive tumors (49%) of which cervical cytology or histology were available in 172 women (85%). Among these, 22 (13%) patients had a cervical history of ≥ IIC. A total of 171 out of 214 women in the HPV-negative group (80%) were examined with cytology and 17 had a history of ≥ IIC. No significant difference in diagnoses of (pre)cancerous lesions between the OPSCC HPV-positive and negative groups were observed (χ2 test p = .28, Fischer's exact test p = .29). CONCLUSION: HPV status in oropharyngeal tumors was not correlated with a history of ≥ IIC in cervical examinations. The effect on cervical dysplasia may be masked by a higher incidence of smoking among the OPSCC HPV-negative group.

Ferritin heavy chain in triple negative breast cancer: a favorable prognostic marker that relates to a cluster of differentiation 8 positive (CD8+) effector T-cell response.

Ferritin heavy chain (FTH1) is a 21-kDa subunit of the ferritin complex, known for its role in iron metabolism, and which has recently been identified as a favorable prognostic protein for triple negative breast cancer (TNBC) patients. Currently, it is not well understood how FTH1 contributes to an anti-tumor response. Here, we explored whether expression and cellular compartmentalization of FTH1 correlates to an effective immune response in TNBC patients. Analysis of the tumor tissue transcriptome, complemented with in silico pathway analysis, revealed that FTH1 was an integral part of an immunomodulatory network of cytokine signaling, adaptive immunity, and cell death. These findings were confirmed using mass spectrometry (MS)-derived proteomic data, and immunohistochemical staining of tissue microarrays. We observed that FTH1 is localized in both the cytoplasm and/or nucleus of cancer cells. However, high cytoplasmic (c) FTH1 was associated with favorable prognosis (Log-rank p = 0.001), whereas nuclear (n) FTH1 staining was associated with adverse prognosis (Log-rank p = 0.019). cFTH1 staining significantly correlated with total FTH1 expression in TNBC tissue samples, as measured by MS analysis (Rs = 0.473, p = 0.0007), but nFTH1 staining did not (Rs = 0.197, p = 0.1801). Notably, IFN γ-producing CD8+ effector T cells, but not CD4+ T cells, were preferentially enriched in tumors with high expression of cFTH1 (p = 0.02). Collectively, our data provide evidence toward new immune regulatory properties of FTH1 in TNBC, which may facilitate development of novel therapeutic targets.

Annexin A2 and S100A10 as Candidate Prognostic Markers in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Ovarian cancer (OC) is the 5th most common cancer among European women. Approximately 70-80% of OC is diagnosed at advanced stage resulting in an elevated mortality rate. The aim of this study was to examine whether Annexin A2 and S100A10 expression can be used as prognostic markers for epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Expression of Annexin A2 and S100A10 was evaluated in EOC tissue samples (n=303) by immunohistochemistry. The staining of the membrane, cytoplasmic and stroma was assessed according to intensity. RESULTS: The expression of both markers correlated to histological subtype, histological grading, International Federation of Gynecology and Obstetrics (FIGO) stage, and macro-radical surgery. Univariate Cox regression analysis showed that Annexin A2 and S100A10 in stromal tissue correlated with shorter overall survival (OS). Multivariate Cox regression analysis demonstrated no independent prognostic significance of stromal Annexin A2 expression. CONCLUSION: High expression of Annexin A2 and S100A10 in stromal tissue from EOC patients was associated with reduced OS; however, no independent prognostic value was found for any of the markers.

Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.

We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules.

Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients.

Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung and gastrointestinal tract combined with positive neuroendocrine immunohistochemical markers. While much information has been gathered during the last decade, most studies suffer from poor statistics due to a low incidence, and there are still fundamental open questions regarding etiology and prognosis. Furthermore, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features.

Tissue microarray analysis as a screening tool for neuroendocrine carcinoma of the breast.

Neuroendocrine carcinoma of the breast (NCB) is a fairly recent diagnostic entity added by WHO in 2003. Since then, studies have indicated that NCB potentially displays a worse prognosis than invasive ductal carcinoma. However, due to a lack of standard use of immunohistochemical staining for neuroendocrine markers and the fact that NCB may only show slight neuroendocrine morphology that can easily be overlooked, NCB is often underdiagnosed. Consequently, there is a need for fast and reliable detection method for NCB. Here, we take a first step toward finding an easy way of identifying NCB by investigating the usefulness of tissue microarray (TMA) analysis as a screening tool. We present our findings with regard to sensitivity and specificity compared with whole-mount sections. The material consists of 240 cases of breast cancer divided into 20 TMA blocks that were all immunohistochemically stained for the neuroendocrine markers chromogranin A and synaptophysin. Cases positive in more than 50% of the tumor cells were accepted in accordance with WHO (2003) standards of NCB. Sensitivity and specificity for TMA sections vs whole-mount sections were found to be 100% and 97.8%, respectively, suggesting that TMA analysis is a reliable method for NCB detection.