scholarly journals Evaluation of Merkel Cell Polyomavirus DNA in Tissue Samples from Italian Patients with Diagnosis of MCC

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 61
Author(s):  
Carla Prezioso ◽  
Raffaella Carletti ◽  
Francisco Obregon ◽  
Francesca Piacentini ◽  
Anna Maria Manicone ◽  
...  
Keyword(s):  
Point Mutations ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Metastatic Lesions ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Metastatic Sites ◽  
Archived Specimens ◽  
Coding Control

Because the incidence of Merkel cell carcinoma (MCC) has increased significantly during the last 10 years and it is recognized that Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis, this study investigated the detection of MCPyV in skin and lymph nodes with histological diagnosis of MCC. Formalin-fixed paraffin-embedded tissue (FFPE) were retrieved from archived specimens and MCPyV non-coding control region (NCCR) and viral capsid protein 1 (VP1) sequences were amplified and sequenced. Results provide an interesting observation concerning the discrepancy between the MCPyV DNA status in primary and metastatic sites: in fact, in all cases in which primary and metastatic lesions were investigated, MCPyV DNA was detected only in the primary lesions. Our data further support the “hit-and-run” theory, also proposed by other authors, and may lead to speculation that in some MCCs the virus is only necessary for the process of tumor initiation and that further mutations may render the tumor independent from the virus. Few point mutations were detected in the NCCR and only silent mutations were observed in the VP1 sequence compared to the MCPyV MCC350 isolate. To unequivocally establish a role of MCPyV in malignancies, additional well-controlled investigations are required, and larger cohorts should be examined.

Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1085-1085
Author(s):  
Azadeh Nasrazadani ◽  
Yujia Li ◽  
George Tseng ◽  
Jennifer Xavier ◽  
Adrian V. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chest Wall ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Lobular Carcinoma ◽  
Metastatic Lesions ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Mixed Histology ◽  
Metastatic Sites

1085 Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p < 0.001), and less likely to have metastasis to the peritoneum (p < 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.

scholarly journals TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Tert Promoter Mutations ◽  
Formalin Fixed Paraffin Embedded ◽  
Penile Squamous Cell Carcinoma ◽  
Promoter Mutations

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

scholarly journals The Dutch National TissueArchive Portal enables efficient, consistent, and transparent procurement of diagnostic tissue samples for scientific use

2021 ◽  
Author(s):  
Robin Verjans ◽  
Annette H. Bruggink ◽  
Robby Kibbelaar ◽  
Jos Bart ◽  
Aletta Debernardi ◽  
...  
Keyword(s):  
The Netherlands ◽  
Tissue Sample ◽  
Ffpe Tissue ◽  
Tissue Samples ◽  
Internet Portal ◽  
Formalin Fixed Paraffin ◽  
Practical Support ◽  
Formalin Fixed Paraffin Embedded ◽  
The Rich ◽  
Formalin Fixed

AbstractBiobanks play a crucial role in enabling biomedical research by facilitating scientific use of valuable human biomaterials. The PALGA foundation—a nationwide network and registry of histo- and cytopathology in the Netherlands—was established to promote the provision of data within and between pathology departments, and to make the resulting knowledge available for healthcare. Apart from the pathology data, we aimed to utilize PALGA’s nationwide network to find and access the rich wealth of Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples for scientific use.  We implemented the Dutch National TissueArchive Portal (DNTP) to utilize PALGA’s nationwide network for requesting FFPE tissue samples. The DNTP consists of (1) a centrally organized internet portal to improve the assessing, processing, harmonization, and monitoring of the procurement process, while (2) dedicated HUB-employees provide practical support at peripheral pathology departments. Since incorporation of the DNTP, both the number of filed requests for FFPE tissue samples and the amount of HUB-mediated support increased 55 and 29% respectively. In line, the sample procurement duration time decreased significantly (− 47%). These findings indicate that implementation of the DNTP improved the frequency, efficiency, and transparency of FFPE tissue sample procurement for research in the Netherlands. To conclude, the need for biological resources is growing persistently to enable precision medicine. Here, we access PALGA’s national, pathology network by implementation of the DNTP to allow for efficient, consistent, and transparent exchange of FFPE tissue samples for research across the Netherlands.

Antitumor immune response is associated with favorable survival in GEP-NEN G3

2021 ◽  
Vol 28 (10) ◽  
pp. 683-693
Author(s):  
Vivian Rosery ◽  
Henning Reis ◽  
Konstantinos Savvatakis ◽  
Bernd Kowall ◽  
Martin Stuschke ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Spatial Interaction ◽  
Antitumor Immune Response ◽  
Cytotoxic T Cell ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

The tumor immune microenvironment (TME) represents a key determinant for responses to cancer treatment. However, the immune phenotype of highly proliferative gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is still largely elusive. In this retrospective study, we characterized the TME of high-grade (G3, Ki-67 > 20%) GEP-NEN. We analyzed formalin-fixed paraffin-embedded samples from 37 patients with GEP-NEN G3 by immunohistochemistry and multiplex immunofluorescence to address the abundance and spatial interaction of relevant immune subsets. We focused on the expression of immune checkpoint molecules PD-1 and PD-L1, the cytotoxic T-cell marker CD8, and the tumor-associated macrophage marker CD206. Findings were correlated with overall survival (OS) from the date of a cancer diagnosis. Patients with PD-L1-positive tumors (CPS ≥ 1) and intense PD-1+CD8+ immune cell infiltration showed the most favorable median OS. Multiplex immunofluorescence staining of ten representative tissue samples illustrated intratumoral heterogeneity of PD-L1 expression. Dense PD-1+CD8+ immune cell infiltrates were observed in PD-L1-positive tumor regions but not in PD-L1-negative regions. Proximity analysis revealed a spatial interaction between PD-1+CD8+ cells and PD-L1-positive cells. Our data suggest a pre-existing antitumor immune response in the TME in a subgroup of GEP-NEN G3. This supports a targeted clinical exploration of immunotherapeutic approaches.

Microsatellite instability evaluation: which test to use for endometrial cancer?

2021 ◽  
pp. jclinpath-2021-207723
Author(s):  
Paola Rafaniello-Raviele ◽  
Ilaria Betella ◽  
Alessandra Rappa ◽  
Davide Vacirca ◽  
Gianluca Tolva ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Automated System ◽  
Tissue Samples ◽  
Valuable Alternative ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Mmr Proteins

AimsAnalysis of microsatellite instability (MSI) is strongly recommended in endometrial cancer (EC) and colorectal cancer to screen for Lynch syndrome, to predict prognosis and to determine optimal treatment and follow-up. In a large monoinstitutional series of ECs, we evaluated the reliability and accuracy of Idylla assay, a rapid, fully automated system to detect MSI, and we compared its performance with two routine reference methods.MethodsWe evaluated MSI status in 174 formalin-fixed, paraffin-embedded EC tissue samples using immunohistochemistry (IHC) for mismatch repair (MMR) proteins and Idylla assay. Samples with discordant or equivocal results were analysed with a third technique, the Promega MSI kit.ResultsIdylla MSI assay and IHC were highly concordant (overall agreement: 154/170=90.59%, 95% CI 85.26% to 94.12%). However, in four samples, MMR-IHC staining was equivocal; moreover, 16 cases showed discordant results, that is, MMR deficient using IHC and microsatellite stable using Idylla. These 20 samples were reanalysed using the MSI-Promega kit, which showed the same results of Idylla assay in 18/20 cases (overall agreement: 90%, 95% CI 69.90% to 97.21%).ConclusionsOur results suggest that IHC is an efficient method to determine MMR status in ECs. However, the Idylla MSI assay is a rapid and reliable tool to define MSI status, and it could represent a valuable alternative to conventional MSI-PCR methods.

scholarly journals Evaluation of Formalin-fixed Paraffin-embedded Tissue Samples Diagnosed by Histopathology as Echinococcus in Çorum

2021 ◽  
Vol 45 (4) ◽  
pp. 262-267
Author(s):  
Yılmaz Baş ◽  
Yunus Emre Beyhan ◽  
Havva Hande Keser Şahin ◽  
Tuğba Özçerezci ◽  
Dursun Karasartova ◽  
...  
Keyword(s):  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed
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