Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I: <2500 μm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 μm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage . In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p < 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection. Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 16 November 2020; doi:10.1038/s41379-020-00709-2 Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Our study aimed to validate the clinicopathological characteristics and prognosis of lung adenocarcinoma (ADC) with a filigree pattern and to further investigate the relationship between the filigree pattern and the classical micropapillary (MP) pattern. We retrospectively reviewed the clinical and pathologic characteristics of 461 Chinese patients with completely resected ADC (stage I, 310; stage II, 44; stage III, 107). The filigree pattern was more likely to be observed in ADC with a higher stage (p = 0.003) and the classical MP pattern (p < 0.001). Patients with filigree-predominant ADC showed poor survival, similar to those with classical MP-predominant ADC. Multivariate analysis confirmed that the presence of the filigree pattern was an independent prognostic factor for recurrence-free survival (hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.50–2.68; p < 0.001) and overall survival (OS; HR, 1.83; 95% CI, 1.34–2.50; p < 0.001). Patients with both cl assical MP-positive and filigree-positive ADC had the worst survival compared with those with the filigree pattern or classical MP pattern alone. In stage I, ADC with both the filigree and classical MP patterns had a higher incidence of micrometastasis than ADC with the filigree pattern or classical MP pattern alone. Lymph node micrometastasis indicated poor survival in patients with ADC with the filigree pattern or classical MP pattern. Similar clinicopathologic features between patients with the filigree pattern and the classical MP pattern support the inclusion of the filigree pattern in the MP category. Recognition of the filigree pattern could provide helpful prognostic information, especially for stage I ADC. Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 16 November 2020; doi:10.1038/s41379-020-00711-8 Recognition of filigree pattern expands the concept of micropapillary subtype in patients with surgically resected lung adenocarcinoma View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy-number losses were detected; overall, nearly all tumors (n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy-number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2, CCND1, MYC, FGFR1, and EGFR copy-number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR, KRAS, and CDKN2A mutations, TERT copy-number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer. <i>TP53</i> mutations and <i>CDKN2A</i> mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 17 November 2020; doi:10.1038/s41379-020-00716-3 TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Renal cell carcinomas with t(6;11) chromosome translocation has been classically characterized by the rearrangement of the TFEB gene, located on chromosome 6, and MALAT1 gene, located on chromosome 11. Recently, a few other genes have been described as fusion partners in TFEB rearranged renal cell carcinomas. Although most of TFEB rearranged renal cell carcinomas have an indolent behavior, in the rare cases of advanced metastatic disease targeted therapy and predictive markers remain lacking. In the present study, we collected 13 TFEB rearranged renal cell carcinomas, confirmed by FISH, analyzing their morphology and exploring the novel gene partners. Looking for predictive markers, we have also performed PDL1 immunohistochemical analysis by using four different assays (E1L3N, 22C3, SP142, and SP263). MALAT1 gene rearrangement has been found in ten tumors, five cases showing classical biphasic morphology with "rosettes", five cases without "rosettes" mimicking other renal cel l carcinomas or epithelioid angiomyolipoma/pure epithelioid PEComa. We identified two different partner genes, ACTB and NEAT1, the latter previously unreported and occurring in a tumor with an unusual solid and cystic appearance. In both cases, the "rosettes" were absent. In one case no gene partner was identified. Overall, in 12 of 13 TFEB-rearranged renal cell carcinomas staining for PDL1 SP263 was observed, whereas the other antibodies were less reliable or more difficult to interpret. In conclusion, we described the third case of ACTB-TFEB rearranged renal cell carcinoma and a novel NEAT1-TFEB rearranged renal cell carcinoma, both without the distinctive biphasic morphology typical of t(6;11) renal cell carcinoma. Finally, PDL1 SP263 was constantly expressed in TFEB rearranged renal cell carcinoma with possible clinical benefit which requires further investigations. <i>TFEB</i> rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring <i>MALAT1-TFEB, ACTB-TFEB,</i> and the novel <i>NEAT1-TFEB</i> translocations constantly express PDL1 Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 18 November 2020; doi:10.1038/s41379-020-00713-6 TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. This included 242 (36.4%) patients with hormone receptor (HR)+/HER2− cancers, 216 (32.5%) with HER2+ tumors, and 207 (31.1%) with triple negative breast cancer (TNBC). Slide review was blinded to pre-treatment clinico-pathologic features. pCR was achieved in 7.9%, 37.0%, and 37.7%, of HR+/HER2− cancers, HER2+ cancers, and TNBC respectively (p < 0.001). Among 389 patients with residua l invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8%) had a scattered pattern and 102 (26.2%) had a circumscribed pattern. In both univariate and multivariate analyses, there was a significant association between tumor subtype and pattern of response. Among patients with HR+/HER2− tumors, 89.4% had a scattered pattern and only 10.6% had a circumscribed pattern. In contrast, among those with TNBC 52.8% had a circumscribed pattern and 47.2% had a scattered pattern (p < 0.001). In addition to subtype, histologic grade and tumor size at presentation were also significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size each associated with a scattered response pattern (p = 0.002 and p = 0.01, respectively). A better understanding of the relationship between pre-treatment clinico-pathologic features of the tumor and pattern of residual disease may be of value for helping to guide post- chemotherapy surgical management. Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 20 November 2020; doi:10.1038/s41379-020-00714-5 Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer

xloma.fota.13 shared this article with you from Inoreader Message: Abstract Tumor proportion score (TPS) and combined positive score ([CPS] includes immune cells), 2 methods for scoring programmed death ligand 1 (PD-L1) expression, have been used in clinical trials investigating the immune checkpoint inhibitor pembrolizumab in head and neck squamous cell carcinoma (HNSCC). These trials resulted in regulatory approval for pembrolizumab in the first- and second-line setting outside the United States. We performed a post hoc analysis of the KEYNOTE-040 study (NCT02252042) to determine whether CPS is a practical and suitable alternative scoring method to TPS. In KEYNOTE-040, patients with metastatic HNSCC received pembrolizumab or investigator choice of standard of care (SOC). The relative utility and equivalence of CPS ≥ 50 and TPS ≥ 50% for defining PD-L1 expression status in patients with HNSCC and comparability of scoring methods by tandem receiver operating characteristic (ROC) analysis were analyzed. The cutoff for each method was also evaluate d. CPS ≥ 50 appeared equivalent to TPS ≥ 50% for predicting objective response rate (ORR), overall survival, and progression-free survival. ORR for pembrolizumab versus SOC was 26.2 versus 8.5% for TPS ≥ 50%, 28.1 versus 7.7% for CPS ≥ 50, 10.6 versus 11.6% for TPS < 50%, and 10.0 versus 12.0% for CPS < 50. Tandem ROC analysis showed that TPS 50% and CPS 50 maximized delta Youden index and suggested that CPS is more sensitive than TPS at lower cutoffs (i.e., CPS ≥ 1). In conclusion, CPS 50 can be used interchangeably with TPS 50% to determine PD-L1 status in patients with HNSCC. CPS may be more sensitive than TPS at lower cutoffs. Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer Via Modern Pathology - AOP - nature.com science feeds Modern Pathology, Published online: 25 November 2020; doi:10.1038/s41379-020-00710-9 Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reference Intervals of Total Testosterone

alkiviadis.1961 shared this article with you from Inoreader Reference Intervals of Total Testosterone in Adult Filipino Men Via Hindawi Publishing Corporation Background. The reference range of total testosterone needs to be established locally as ethnic differences in adiposity, insulin sensitivity, and sex hormone-binding globulin (SHBG) levels may affect total testosterone levels. The aim of this study is to establish the reference intervals of total testosterone from healthy, young adult Filipino males. Methods. The study included 110 healthy, Filipino male volunteers aged 21–40, studying or working at the University of the Philippines Manila. Clinical history, height, weight, body mass index (BMI), and blood pressure (BP) were obtained, and blood for total testosterone, SHBG, albumin, insulin, fasting blood sugar (FBS), and total cholesterol was collected. Free testosterone was calculated using Vermeulen's formula. The 2.5th to 97.5th percentiles of subjects for total testosterone were used as the normative range for Filipino men. Results. The reference range of total testosterone is 7.33–53.01 nmol/L. Conclusion. The pr esent study derived reference ranges of total testosterone using data from apparently healthy, young adult men to support clinical services. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.