News Update on Neuroendocrine Carcinoma Research: April – 2019
Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma
Aim
Primary cutaneal system cancer, or Merkel cell cancer (MCC), can not be distinguished morphologically from small‐cell system carcinomas (SmCC) from alternative sites. assay is needed to substantiate cutaneal origin, and is additionally used for detection of watcher lymphoid tissue (SLN) metastases of MCC. Cytokeratin twenty (CK20) expression is usually used for these functions, however is negative in some MCC cases, and has unclear specificity. we tend to evaluated assay for neurofilament and CK20 in MCC compared with SmCC from alternative sites.
Methods and results
We evaluated neurofilament expression in fifty five MCC specimens from thirty-nine distinctive patients, as well as 9 CK20‐negative MCC tumours. Neurofilament expression was discovered in forty two of fifty five (76.4%) MCC cases, as well as seven of 9 (77.8%) CK20‐negative MCC cases. Neurofilament was expressed in 9 of twelve (75%) Merkel cell polyomavirus‐positive tumours and 5 of ten (50%) virus‐negative tumours. Compared to a customary immunohistochemical panel (cytokeratin cocktail and CK20), neurofilament was eighty seven.5% sensitive for police work SLN metastases. Neurofilament and CK20 expression was additionally assessed in sixty one extracutaneous SmCC from sixty distinctive patients, with primary sites as well as respiratory organ (27), bladder (18), cervix (3), duct (3), sinonasal tract (2) and alternative sites (7). The specificity of neurofilament and CK20 for MCC versus non‐cutaneous SmCC was ninety six.7% and 59.0%, severally.
Conclusions
Neurofilament has superior specificity to CK20 in characteristic MCC from non‐cutaneous SmCC. Neurofilament is usually expressed in CK20‐ and virus‐negative MCC tumours. Limitations of neurofilament assay embrace lower sensitivity than CK20 and refined staining in some tumours. However, our findings indicate that neurofilament is helpful for excluding non‐cutaneous SmCC. [1]
Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas
Merkel cell cancer could be a rare system carcinoma of the skin principally evoked by Merkel cell polyomavirus integration. Cytokeratin twenty (CK20) quality is presently accustomed distinguish Merkel cell carcinomas from different system carcinomas. However, this distinction is also difficult in CK20-negative cases and in cases while not a primary tumor. The objectives of this study were initial to guage the diagnostic accuracy of antecedently delineated markers for the diagnosing of Merkel cell cancer and second to validate these markers within the setting of difficult-to-diagnose Merkel cell carcinoma variants. in a very preliminary set (n = 30), we tend to assessed best immunohistochemical patterns (CK20, thyroid transcription issue one [TTF-1], atonal homolog one [ATOH1], neurofilament [NF], special AT-rich sequence-binding supermolecule a pair of [SATB2], paired box supermolecule five, terminal desoxynucleotidyl enzyme, CD99, mucin 1, and Merkel cell polyomavirus-large T antigen) and Merkel cell polyomavirus load thresholds (real-time PCR). The diagnostic accuracy of every marker was then assessed in a very
validation set of 103 Merkel cell cancers (9 CK20-negative cases and fifteen cases while not a primary skin tumor) and seventy extracutaneous system carcinoma cases. the foremost discriminant markers for a diagnosing of Merkel cell cancer were SATB2, NF expression, and Merkel cell polyomavirus DNA detection (positive chance ratios: thirty six.6, 44.4, and 28.2, respectively). concerning Merkel cell cancer variants, cases while not a primary tumor maintained an analogous immunohistochemical profile and CK20-negative tumors displayed a special profile (decrease frequency of NF and SATB2 expression), however Merkel cell polyomavirus DNA remained detected (78% of cases by qPCR). Moreover, 8/9 (89%) CK20-negative Merkel cell cancer cases however solely 3/61 (5%) CK20-negative extracutaneous system cases were positive for a minimum of one in every of these markers. lastly, detection of SATB2 and NF expression and Merkel cell polyomavirus DNA helps distinguish between Merkel cell cancer classical and variant cases and extracutaneous system carcinomas. [2]
Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast
Introduction
Neuroendocrine cancer (NEC) of the breast may be a rare, special style of carcinoma, reportedly constituting a pair of to five of all breast cancers. though breast necrotizing enterocolitis doesn’t have a selected targeted medical aid, many new targeted therapies supported specific biomarkers were recently investigated within the necrotizing enterocolitis of respiratory organ and in alternative styles of breast cancer, which can give steerage to their practicableness in breast necrotizing enterocolitis.
Materials and ways
Twenty breast NECs were profiled for biomarkers of medical aid together with antibody-drug conjugates (DLL3, TROP-2, and FOLR1), simple protein deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 sequence fusions) targeted inhibitors, alkylating agents (MGMT), and immune stop inhibitors (PD-L1, TMB, and MSI) victimisation assay and DNA/RNA next-generation sequencing assays.
Results
Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in numerous subsets of tumors and will pave the manner for development of novel targeted therapies in some patients with breast NECs. There was no proof of DLL3 expression, NTRK sequence fusions, or MGMT hypermethylation. No biomarkers prognostic of immune stop matter effectivity (programmed death-ligand one expression, neoplasm modification burden, microsatellite instability) were known. FGFR and CCND1 sequence amplifications were detected in isolated cases.
Conclusions
This study known many potential targets for novel therapies in breast necrotizing enterocolitis, together with farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 sequence amplification might indicate the utility of investigational therapies. The reportable results ought to function associate degree early indication of potential clinical connection in hand-picked patients with breast necrotizing enterocolitis. [3]
Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis
The distinction between respiratory organ massive cell system malignant neoplastic disease and tiny cell carcinoma is tough in some cases. Some propose that these malignant neoplastic diseases ought to be classified united top-grade system carcinoma. we tend to examined biological options of tiny cell malignant neoplastic disease (n=23), massive cell system malignant neoplastic disease (n=17), and classic massive cell malignant neoplastic disease (n=12). the common quantitative relation of nuclear diameter of the growth cells thereto of lymphocytes for little cell malignant neoplastic disease was smaller than that for giant cell system carcinoma (P [4]
Role of Tumor Markers in Oral Cancer: An Overview
The oral mucous membrane represents the primary a part of the channel and is exposed to numerous exogenous toxins. Exposure for extended length will cause changes that lead to doubtless malignant diseases or cancers / Tumors. Eventually these are often diagnosed by routine histopathology, however few of them are tough to diagnose by this methodology alone. There arises the role of tumour markers in identifying completely different pathologies is well established. A marker are often delineate as some unnoticeable object wont to distinguish or mark bound things. principally tumour markers are proteins and these markers is also detected among exfoliated or distributed cells, or as current agents among the peripheral blood or plasma. within the recent years, there’s a revived interest concerning tumour markers, providing window of chance for management of cancer patients by enhancing the potency in detection and treatment set up. Recent technological advancement has enabled the examination of the many potential markers. This paper focuses on the tumour markers within the head and neck neoplasm.[5]
Reference
[1] Stanoszek, L.M., Chan, M.P., Palanisamy, N., Carskadon, S., Siddiqui, J., Patel, R.M., Harms, K.L., Lowe, L., Fullen, D.R. and Harms, P.W., 2019. Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma. Histopathology, 74(3), pp.504-513. (Web Link)
[2] Kervarrec, T., Tallet, A., Miquelestorena-Standley, E., Houben, R., Schrama, D., Gambichler, T., Berthon, P., Le Corre, Y., Hainaut-Wierzbicka, E., Aubin, F. and Bens, G., 2019. Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas. Modern Pathology, 32(4), p.499. (Web Link)
[3] Vranic, S., Palazzo, J., Sanati, S., Florento, E., Contreras, E., Xiu, J., Swensen, J. and Gatalica, Z., 2019. Potential novel therapy targets in neuroendocrine carcinomas of the breast. Clinical breast cancer, 19(2), pp.131-136. (Web Link)
[4] Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis
Kenzo Hiroshima, Akira Iyoda, Takashi Shida, Kiyoshi Shibuya, Toshihiko Iizasa, Hirohisa Kishi, Tohru Tanizawa, Takehiko Fujisawa & Yukio Nakatani
Modern Pathology volume 19, pages 1358–1368 (2006) (Web Link)
[5] Lavanya, R., Mamatha, B., Waghray, S., Chaitanya, N., Reddy, M. P. and Bau, D. B. (2016) “Role of Tumor Markers in Oral Cancer: An Overview”, Journal of Advances in Medicine and Medical Research, 15(7), pp. 1-9. doi: 10.9734/BJMMR/2016/24998. (Web Link)