Thyroid Gland Metastasis From Endometrial Carcinoma Causing Acute Severe Dyspnea

Thyroid metastasis from cervical carcinomas is an extremely rare disease; therefore, only a few cases have so far been reported in the literature. Due to the lack of data and the heterogeneity of clinical cases, the percentage of patients affected by thyroid metastases eligible to undergo surgery is not easily predictable. This report describes a rare case of endometrioid adenocarcinoma metastasized to the thyroid gland. A 72-year-old woman was referred to the ENT department of our hospital (Ospedale Degli Infermi di Biella, Italy) presenting with dyspnea and rapidly worsening condition, in need of emergency surgery. The peculiarity of this case lies in the metastasis isotype rarity, in its voluminous dimension, and in its mediastinal localization, which required the intervention of a multidisciplinary team to establish successful treatment planning.

Overview of virus and cancer relationships. Position paper

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

3q26 Amplifications in Cervical Squamous Carcinomas

Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.

E6/E7 Variants of Human Papillomavirus 16 Associated with Cervical Carcinoma in Women in Southern Mexico

Persistent infection with the human papillomavirus 16 (HPV 16) is the cause of half of all cervical carcinomas (CC) cases. Moreover, mutations in the oncoproteins E6 and E7 are associated with CC development. In this study, E6/E7 variants circulating in southern Mexico and their association with CC and its precursor lesions were evaluated. In total, 190 DNA samples were obtained from scrapes and cervical biopsies of women with HPV 16 out of which 61 are from patients with CC, 6 from patients with high-grade squamous intraepithelial lesions (HSIL), 68 from patients with low-grade squamous intraepithelial lesions (LSIL), and 55 from patients without intraepithelial lesions. For all E7 variants found, the E7-C732/C789/G795 variant (with three silent mutations) was associated with the highest risk of CC (odd ratio (OR) = 3.79, 95% confidence interval (CI) = 1.46–9.85). The analysis of E6/E7 bicistron conferred to AA-a*E7-C732/C789/G795 variants revealed the greatest increased risk of CC (OR = 110, 95% CI = 6.04–2001.3), followed by AA-c*E7-C732/C789/G795 and A176/G350*E7-p. These results highlight the importance of analyzing the combinations of E6/E7 variants in HPV 16 infection and suggest that AA-a*E7-C732/C789/G795, AA-c*E7-C732/C789/G795, and A176/G350*E7-p can be useful markers for predicting CC development.

Frequency of Pelvic Lymphatic Metastases in Patients with Cervical Cancer – A Retrospective Study

Introduction and objective: The aim of this study was to determine the incidence of pelvic lymph metastases in cervical cancer, depending on the biology of the tumor and the new changes in the staging. Material and methods: A retrospective database analysis involving 85 patients with cervical carcinoma for a 5-year period was performed. Various factors were analyzed for the purpose of the study. Results: In 20% of our patients lymph metastases were found with more frequent locus in the right lymph chains. The average number of metastases was equal to or greater than 2. Moderately differentiated cervical carcinomas metastasized most commonly. The most frequent were metastases in squamous cell carcinoma and in Stage 2B under the TNM classification. After changes in FIGO’s classification the presence of positive lymph nodes defined the disease as III stage. Conclusion: Our study confirms that cervical carcinoma metastasizes in the pelvic lymph nodes before it reaches the para-aortic lymph nodes.

PI3KCA Mutations in Uterine Cervix Carcinoma

Background: Squamous cervical carcinoma represents an infection-associated malignancy that produces a high mortality when metastatic or recurrent after primary local treatment. There is an urgent need for new therapies for this cancer. Molecular lesions in cervical cancer may provide opportunities for targeted therapies development. Methods: Publicly available data from the Cancer Genome Atlas (TCGA) were analyzed to define the molecular landscape of squamous cervical carcinomas with and without mutations of PIK3CA, the gene encoding the alpha catalytic subunit of phosphatidylinositol 3 kinase (PI3K). Associations with alterations in other critical genes and pathways of cancer and the total mutation burden and copy number alteration burden of cervical cancers were examined. Results: Mutations in PIK3CA are observed in 27.1% of squamous cervical cancers. PIK3CA represents the most frequently mutated gene in these cancers. Mutations in PIK3CA are associated with higher rates of mutations in other genes of important cancer-associated pathways such as the tyrosine kinase receptors/K-Ras/BRAF/MAPK and the Wnt/β catenin pathway. In addition, PIK3CA mutated cervical cancers display a higher tumor mutation burden (TMB) than non-mutated cancers. Conclusion: Frequent mutations of PIK3CA gene in squamous cervical carcinomas may represent an opportunity for targeted therapies development both inhibiting the PI3K kinase and associated pathway defects. Increased TMB may additionally confer immunotherapy sensitivity.

Tumor budding in cervical carcinoma: Associations with some clinical and pathological factors

Background: Tumor budding is recognized as an important independent prognostic factor in colorectal carcinoma. The aim of this study was to evaluate the grade of tumor budding and association with other clinical and pathological features in patients with cervical carcinoma. Material and methods: We evaluated pathohistological data from 91 cervical carcinoma patients (mean age: 53.8 years) who underwent radical hysterectomy and pelvic lymphatic dissection at the Oncology Institute of Vojvodina between January 2010 and December 2018. Tumor budding was evaluated in invasive front of the tumor. Based on the number of bud counts/10 high power field, three groups were formed: with no budding, with less than 15 buds, and with more than 15 buds. Results: Eighty (87.91%) of evaluated cervical carcinomas were squamous-cell type, while 12.09% were adenocarcinomas. All carcinomas were graded (HG1-HG3). Average diameter of the tumors was 25 mm (81.6% < 4 cm and 18.4% > 4 cm). Metastases in lymph nodes were present in 30 (32.9%) cases. Based on the number of bud counts/10 high power field there were 35.1% with no budding, 32.9% with less than 15 buds and 37.3% with more than 15 buds. There was a significant association between tumor budding grade and histological grade (p=0.04), as well as with tumor budding grade and the diameter of the tumor (p=0.04). Conclusion: As a quantitative measure of cancer cell dissociation, tumor budding is associated with poor prognosis in cervical carcinoma and should be considered as a prognostic factor.

Viral load and interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer

<abstract> <p>Cervical cancer is the sequel of a multi-factorial, long-term unresolved disease that includes genetic, epigenetic, and viral components responsible for its development and progression. It is the second most common cancer of females in India. Human papillomavirus (HPV) is considered the primary causative agent of pre-neoplastic and cancerous lesions and 90% of all cervical carcinomas are linked to high-risk HPV type 16 and type 18. Although most HR-HPV infections are asymptomatic, transient, and self-limiting, the persistent infection with a high risk (HR-HPV) may cause precancerous lesions that can progress to cervical cancer. HPV type 16 is the most common HPV in India associated with more than 75% of cervical cancer, followed by HPV type 18 and other high-risk types. Infection with HPV alone is not sufficient for the development of cervical cancer but there is the involvement of some host genetic factors also that are responsible for the development and progression of cervical cancer. This article briefly reviews molecular pathogenesis, viral load, and the interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer.</p> </abstract>