her2 status in premalignant dysplastic gastric lesions

Abstract is not required for Editorialis not required for Editorial (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 6 No. 8, August 2015. ISSN – [0976-3198] Int J Case Rep Images 2015;6(8):530–533. www.ijcasereportsandimages.com Barresi et al. 530 CASE REPORT OPEN ACCESS HER2 status in premalignant dysplastic gastric lesions Valeria Barresi, Antonio Ieni, Giovanni Tuccari The epidermal growth factor receptor family is constituted by four members with similar structures: HER1/erbB1, HER2/erbB2, HER3/erbB3 and HER4/ erbB4. These receptors play an important role in the processes of proliferation and differentiation of normal cells [1]. The binding of the ligand to these receptors causes the creation of homodimers and heterodimers as well as the activation of downstream signaling pathways [1]. Hence, any aberrations in their structure or function can cause transformation of normal cells to malignant cells with consequent tumor development and progression [1]. However, on the basis of results from an international randomized controlled trial (ToGA), the patients with advanced gastric adenocarcinoma (GC) positive for HER2 over-expression could be eligible for a target treatment with trastuzumab [2]. A significant reduction in the risk of mortality was appreciable when trastuzumab was added to the chemotherapy regimen [2]. There is general agreement with regard to a higher HER2 positivity in gastroesophageal junction cancer (24–35%) compared with GC (9.5–21%) [3]. The rate of HER2 immunoreactivity seemed to be vary variable in relation to the different neoplastic histotype of the stomach [4]. Generally, all studies have reported a prevalence of HER2 amplification in advanced GC of Valeria Barresi1, Antonio Ieni1, Giovanni Tuccari1 Affiliations: 1Azienda Ospedaliera Universitaria "Gaetano Martino" and Department of Human Pathology "Gaetano Barresi", Section of Anatomic Pathology, University of Messina, Messina 98123, Italy. Corresponding Author: Giovanni Tuccari, MD, Full Professor of Pathology Department of Human Pathology, "Gaetano Barresi" University of Messina, A.O.U. "Policlinico G. Martino" Pad. D, Via Consolare Valeria, 98125 – MESSINA (Italy); Ph: +39-90-2212539; Fax:+39-90-2928150 E-mail: [email protected] Received: 16 June 2015 Published: 01 August 2015 EdiTO iAlS OPEN A CE S intestinal type (81.6–91%) in comparison with diffuse or mixed ones (4–7.9%) [4]. In addition, a progressive increase in HER2 overexpression has been appreciated moving from the poorly cohesive WHO histotype to mitochondrion-rich adenocarcinomas (MRC), tubular adenocarcinomas and hepatoid carcinomas (HAS), these latter representing the top rate of HER2 positivity, characterized by an extremely poor prognosis [4]. Furthermore, HER2 overexpression was also significantly associated with a high grade, advanced stage and high Ki67-LI value, becoming thus an additional morphological parameter able to affect the mortality of patients with GC [5]. Finally, some investigations have been recently reported regarding the concordance of HER status in primary gastric cancer and corresponding lymph nodes or distant metastases, with either positive or negative conversion in HER2 overexpression [6, 7]. Generally speaking, chronic atrophic gastritis and intestinal metaplasia of the stomach have been regarded to as pre-neoplastic lesions, even if data from literature points towards the existence of other pathways, in which intestinal metaplasia may not play a role, as described by Japanese authors [8]. However, the true precancerous gastric lesion should be considered dysplasia, which includes cellular and structural atypia, also codified under the term intraepithelial neoplasia (IEN), a pathological condition that lies between atrophic gastritis and GC [9]. It is well known, that IEN may develop in the gastric or intestinal metaplastic epithelium and it can be categorized into four categories: indefinite for intraepithelial neoplasia, low-grade intraepithelial neoplasia (LG-IEN), high-grade intraepithelial neoplasia (HG-IEN) and suspicious for invasive cancer [10]. The IEN histological distinction as low or high-grade depends on the severity of architectural and cytological atypia. In LG-IEN, the mucosal structure is only faintly modified maintaining tubular differentiation with the proliferative zone limited to the outward portion, whereas HG-IEN exhibits increasing distortion of the mucosal architecture, resulting in crowded possibly irregular glands with obvious cellular atypia and proliferative activity distributed throughout the lesion [10]. High-grade intraepithelial neoplasia i

An Updated Review of Cribriform Carcinomas with Emphasis on Histopathological Diagnosis and Prognostic Significance

Cribriform is a histopathological term used to describe a neoplastic epithelial proliferation in the form of large nests perforated by many quite rounded different-sized spaces. This growth pattern may be seen in carcinomas arising in different organs, and shows important prognostic implications. Therefore, recent data in literature suggest that cribriform carcinoma is a histologically and clinically distinctive type of tumour that should be separated from other similar tumour types. In this article, the pathology of cribriform adenocarcinoma of the prostate, lung, breast, stomach, colon, thyroid, and skin is discussed with particular reference to morphologic and immunohistochemical features, differential diagnosis, and clinical behaviour

Pleural diffuse mesothelial lesions: A challenge for pathologists

Malignant mesothelioma (MM) is a highly aggressive tumor deriving from the mesothelial cells normally lining the body cavities.  Histologically, MM is classified in three major histopathological patterns, such as epithelioid, sarcomatoid and mixed type. It is well known that the diagnosis of MM can be very challenging, especially in small bioptic fragments or cytological specimens. The most common diagnostic pitfalls involve the distinction between primary epithelioid MM and metastatic adenocarcinoma as well as that between reactive epithelial/fibrous benign proliferations and MM. Recently, a pathologist’s panel suggested new practical strategies and recommendations for the MM diagnosis, regarding the interpretation of histo-cytological features and the composition of appropriate immunohistochemical algorithm. Finally, according to the updated international guidelines, morphological data require a careful clinico-pathological correlation to achieve an accurate diagnosis of pleural lesions

Rare histotypes of epithelial biliary tract tumors: A literature review

Adenocarcinoma represents the most frequent biliary tract cancer. However, other rare histotypes can be found in the biliary tract, such as cholangiolocellular carcinoma, cholangiocarcinoma with ductal plate malformation pattern, adenosquamous carcinoma, mucinous carcinoma, signet ring cell carcinoma, clear cell carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, and sarcomatous cholangiocarcinoma. These cancer types account for less than 10 % of all the already rare biliary tract tumors. Yet, they represent a relevant issue in everyday clinical practice, given the lack of therapeutic recommendations and the overall scarcity of data, mainly deriving from isolated small center-specific cohorts of patients.The shifts of such histotypes from the most common ones reflect genetic and molecular differences, determine changes in clinical aggressiveness, and suggest a possible variability in sensitivity to the standard treatments of biliary adenocarcinomas. The consistency and degree of these variables are still to be solidly demonstrated and investigated. Therefore, this paper aims to review the current literature concerning very infrequent and rare epithelial biliary tract cancers, focusing our attention on the clinical, molecular, and immunohistochemical features of these tumors

Immunohistochemical evidence of Aquaporin 1 (AQP1) in Fluoroedenite-induced mesotheliomas: a preliminary report

Malignant pleural mesothelioma (MPM) is a malignant tumour of the serosal membranes lining the pleural cavity, which has been linked with the occupational exposure to asbestos fibres; however, it rarely occurs in individuals not exposed to these fibres. In this regard, fluoroedenite (FE) fibres have been linked to increased mortality from pleural mesothelioma in Biancavilla, a town of eastern Sicily (Italy). These fibres are similar in size and morphology to amphibolic asbestos fibres and have been used as a building material for road paving and buildings in the town of Biancavilla and countries nearby. The aim of the present study was to investigate the immunohistochemical expression of Aquaporin 1 (AQP1) in a cohort of patients affected by MPM; taking into consideration its suggested independent prognostic role in asbestos related MPM, the possible correlation with clinicopathological parameters and patients outcomes was also evaluated

HER2 status in advanced gastric cancer: the dark side of the moon

The present study evaluated HER2 status between primary gastric and paired metastatic disease to lymph nodes, collecting 62 formalin-fixed paraffin-embedded representative tissue blocks as well as synchronous metastatic lymph nodes by immunohistochemistry and FISH. The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.26% in primary gastric carcinoma and corresponding nodal metastasis. Moreover, a high level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was achieved in 90.74% of cases. In our opinion, the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity. In any case, the shift from positive to negative HER2 expression suggests that Trastuzumab could be the targeted treatment choice, while the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes

DBBC VLBI2010

The Digital Base-Band Converters-2 (DBBC2) backend system has been adapted for supporting the VLBI2010 demands. The system architecture for this application is presented

DBBC2 Backend: Status and Development Plan

The Digital Base Band Converter-2 (DBBC2) system is in a mature phase now, and the deployment is continuing. A review of the backend is shown, and the new functionalities in development are reported

Colorectal carcinoma grading quantified by counting poorly differentiated clusters: is it feasible on endoscopic biopsies?

no abstract availabl

lmmunohistochemical detection of metallothionein in carcinomatous and normal human gastric mucosa

Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT) expression has been immunohistochemically investigated in 112 formalin-fixed paraffin-embedded surgical gastric samples, 38 of which were early carcinomas (EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data (ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa) were also analysed; in addition, 22 biopsies of normal gastric mucosa were studied as tissue control. The MT immunoreactivity was evaluated by staining and intensity-distribution scores. A various MT positivity was appreciable in the cytoplasm and nucleus of antrum or body gastric epithelia1 cells in 100% of normal control biopsies. 751112 (67%) gastric carcinomas showed MT immunoreactivity with a significant lower expression in AGC. No relationships were encountered between MT immunostaining and clinico-pathological data; in addition, no difference in the Kaplan-Meier survival curves of patients with various MT expression was achieved. When the transitional mucosa was examined, 84/89 (94%) samples were stained although the immunoreaction was not always concordant with that encountered in adjacent carcinomatous elements. The significant statistical decrease of MT scores observed by us moving from normal to neoplastic gastric mucosa allows us to exclude the hypothesis of an overexpression of MT in gastric carcinomas