Significance of transcriptionally-active high-risk human papillomavirus in sinonasal squamous cell carcinoma: Case series and a meta-analysis.

Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in ~25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (~32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.

[A new perspective on axillary dissection in situations of metastatic sentinel node]. / Nový pohled na exenteraci axily pri metastáze v sentinelové uzline.

INTRODUCTION: Breast cancer is the most common malignant disease in women and represents a worldwide problem. Up-to-date diagnostics methods, mammography screening and complex treatments have resulted in a substantial reduction of mortality rates. However, the incidence of the disease keeps growing constantly, although in a moderate way. The struggle against this disease has several levels, such as prevention, primary tumour therapy as well as the management of recurrent or generalized disease. Therefore, it is very significant to evaluate the prognosis on the basis of biological characteristics of the tumour and to determine the right individual therapy in each patient. AIM OF THE STUDY: Our aim was to determine a group of patients with malignant breast disease based on biological characteristics of the tumour who can be treated without axillary exenteration even with a metastasis in the sentinel lymph node, thereby reducing the morbidity associated with this surgery, without worsening the prognosis. METHOD: The research project lasted from June 2012 to June 2015. It was a prospective randomized study where the main investigated group consisted of women with primarily surgically treated mammary cancer undergoing sentinel lymph node biopsy (SNB) during their surgery. These patients were divided into three groups: group 1 - positive SNB without axillary exenteration (axillary dissection - AD); group 2 - positive SNB with AD; and group 3 - negative SNB. Group 4 consisted of patients with primarily performed AD. We investigated statistically significant prognostic factors of metastatic lymph nodes and early disease progression. The results were statistically processed and differences between individual groups were evaluated, determining prognostically usable biological characteristics of the tumour in connection with metastases in lymph nodes and progression-free survival. RESULTS: The study included 214 patients with breast cancer. No metastases of axillary lymph nodes were found in 136 patients (64%); on the other hand, 78 patients (36%) had positive axillary lymph nodes and included: 28 (13%) patients with a micrometastasis in the sentinel lymph node; 38 (17%) patients with 13 positive lymph nodes; 8 (4%) patients with 49 positive lymph nodes; and 4 (2%) patients had more than 10 metastatic lymph nodes. A statistically significant difference with respect to metastatic lymph node involvement was found for the tumour size, expression of oestrogen receptors, proliferative activity and grading. CONCLUSION: The following prognostic factors of metastatic lymph nodes and early disease progression were shown to be statistically significant: tumour size over 2 cm, negative expression of oestrogen receptors, tumours with moderate and high proliferative activity, and tumour grades G2 and G3. In the course of the three years of this study, no regional recurrence was found in axillary lymph nodes in any patient, and therefore, it clearly follows that the completion of axillary exenteration can be omitted in the case of tumour sizes below 2 cm, present expression of oestrogen receptors, low proliferative activity and grade 1 even if one or two positive sentinel lymph nodes are present, provided that adjuvant radiation therapy can be used. Also, axillary exenteration is not needed if a micrometastasis or isolated tumour cells are found in the sentinel lymph node.Key words: breast cancer - sentinel lymph node biopsy - axillary exenteration - prognostic factors.

[Breast Cancer in Young Women - Correlation of Clinical Histomorphological, and Molecular-genetic Features of Breast Carcinoma in Women Younger than 35 Years of Age]. / Karcinom prsu u mladých zen - korelace klinických, histomorfologických a molekulárne-genetických nálezu karcinomu prsu u zen mladsích 35 let.

BACKGROUND: Worldwide, breast cancer is the leading type of malignancy in women. For premenopausal women, the disease brings much higher risk as it is usually more aggressive with worse prognosis. PATIENTS AND METHODS: In this retrospective study, 92 women treated at the Department of Oncology and Radiotherapy in Pilsen were selected from a basic cohort of 356 women under 35 years of age with breast cancer who were diagnosed between 2006 and 2015. The control group comprised 100 postmenopausal women over 65 years of age who were treated for invasive breast cancer. RESULTS: Overexpression of HER2/neu protein and a triple-negative immunoprofile and basal-like phenotype of cancer were more frequently seen in the women under 35 years of age. In addition, malignant cells were poorly differentiated and more aggressive, and prognostically favourable types were not often seen, in these women. In terms of the course of disease, the outcome was worse for the younger patients, and complete remission was reached less frequently and more cases of advanced disease and death due to the malignancy were detected. CONCLUSION: The incidence of invasive breast cancer in young women is low, representing around 2% of all cases of the disease, but this group of patients is prognostically very important. The cancers at such a young age are usually more aggressive (higher mitotic activity and higher grade), and prognostically worse types, such as triple-negative or basal-like, are seen significantly more often in younger patients. This retrospective study confirmed this premise. Moreover, breast cancer in young women is more often associated with genetic predisposition (e.g., hereditary mutations in BRCA1 and BRCA2 genes) than in older women.Key words: breast cancer - young women - triple negative breast cancer - BRCA mutation - basal-like - tumor-suppressor genes This work was partially supported by the Charles University research fund (project number SVV-2016-260 282). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 10. 1. 2017Accepted: 15. 3. 2017.