ABSTRACT
Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.
ABSTRACT
INTRODUCTION: In patients with laryngeal invasive epidermoid carcinoma who are candidates for total laryngectomy, it is recommended to resect en bloc at least half of the thyroid gland on the same side as the laryngeal tumor with the objective of decreasing local recurrence associated with thyroid infiltration. Nevertheless, in the histopathologic analysis of the specimen, a minority of thyroid glands show tumor infiltration. The fact that in these patients even partial thyroid resection is associated with hypothyroidism increased by postoperative radiotherapy is well known. The study was undertaken to determine the frequency of thyroid gland invasion in patients who have undergone total laryngectomy due to laryngeal cancer and its associated factors. MATERIAL AND METHODS: We evaluated the histological results of glands resected en bloc with laryngectomy in patients who underwent total laryngectomy due to laryngeal cancer; the clinical stage was compared to the laryngeal subsite tumor origin. The glandular histological condition was compared to the local recurrence presence (peristomal). RESULTS: Ninety two patients were included, 11 (12%) showed glandular infiltration due to epidermoid carcinoma, all with tumors clinically typified as T3 and T4, 8/11 were transglottic and only 3 (27%) showed subglottic invasion. During follow-up (5-year mean) 17/92 showed peristomal recurrence (18%), only 3 (3%) showed thyroid invasion. Among patients with glandular invasion the peristoma recurrence rate was 27% (3/11). DISCUSSION: The best laryngeal cancer thyroid tumor invasion predictor is the evidence of extralaryngeal extension. Thyroid resection en bloc should not be routinely advised due to the low frequency of glandular infiltration.
