Sequence analysis and transcript expression of the MEN1 gene in sporadic pituitary tumours

The majority of pituitary tumours are monoclonal in origin and arise sporadically or occasionally as part of multiple endocrine neoplasia type 1 (MEN1). Whilst a multi-step aetiology involving both oncogenes and tumour suppressor genes has been proposed for their development, the target(s) of these changes are less clearly defined. Both familial and sporadic pituitary tumours have been shown to harbour allelic deletion on 11q13, which is the location of the recently cloned MEN1 gene. We investigated 23 sporadic pituitary tumours previously shown to harbour allelic deletion on 11q13 with the marker PYGM centromeric and within 50 kb of the MEN1 locus. In addition, the use of intragenic polymorphisms in exon 9 and at D11S4946, and of telomeric loci at D11S4940 and D11S4936, revealed that five of 20 tumours had loss of heterozygosity (LOH) telomeric to the menin gene. However, the overall pattern of loss in informative cases was indicative of non-contiguous deletion that brackets the menin gene. Sequence analysis of all MEN1 coding exons and flanking intronic sequence, in tumours and matched patient leucocyte DNA, did not reveal mutation(s) in any of the 23 tumours studied. A benign polymorphism in exon 9 was encountered at the expected frequency, and in seven patients heterozygous for the polymorphism the tumour showed retention of both copies of the menin gene. Reverse transcription polymerase chain reaction analysis of ten evaluable tumours and four normal pituitaries revealed the presence of the menin transcript. Whilst these findings suggest that gene silencing is unlikely to be mechanistic in sporadic pituitary tumorigenesis, they do not exclude changes in the level or stability of the transcript or translation to mature protein. Our study would support and extend very recent reports of a limited role for mutations in the MEN1 gene in sporadic pituitary tumours. Alternatively, these findings may point to an, as yet, unidentified tumour suppressor gene in this region

Sponge epibionts on ecosystem-engineering ascidians: The case of Microcosmus sabatieri

The study of epibionts on habitat engineering ascidians is of increasing interest because changes in the population structure of the latter may affect associated communities, especially in the case of commercially exploited species. The solitary ascidian Microcosmus sabatieri lives on rocky cliffs in the Eastern Mediterranean and is harvested in certain Aegean areas. Its hard, wrinkled tunic is usually fouled by various epibionts both sessile and motile. Sponges are an important component of this complex and their biomass may be higher than that of the ascidian itself, strongly affecting diversity and abundance of the motile epifauna. The aim of this study was to examine in detail the structure of the epibiotic sponge assemblage on ascidians collected from their main fishing grounds in the South Aegean Sea. A rich (41 species) and taxonomically diverse sponge assemblage was found, while only eight species contributed 80% of the total sponge cover. Most of the epibiotic sponges commonly grow on the surrounding sublittoral cliffs. The encrusting sponge growth form prevailed in cover of the ascidian tunic, while two massive species dominated in terms of frequency of appearance and abundance. Ascidian dimensions, weight and volume were significantly correlated with sponge diversity, abundance and cover area, thus structuring the epibiotic sponge assemblage. Spatial patterns in sponge cover were not clear, but a general declining NW to SE trend in sponge richness, abundance and cover appeared in accordance with previous records. Sponge distribution on the ascidian tunic presented a clear pattern related with characteristic features of the ascidian: the posterior zone supported the richest and most expansive sponge fauna. The ecosystem-engineering process performed by the ascidian is enhanced by the diverse epibiotic sponge assemblage, thus further increasing habitat complexity in this space-limited, temperate, sublittoral, rocky environment. (C) 2009 Elsevier Ltd. All rights reserved

Surgical treatment of potentially primary malignant adrenal tumors: An unresolved issue

Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors. The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality. © 2015, Hellenic Endocrine Society. All rights reserved

Endocervical glandular lesions: A diagnostic approach combining a semi-quantitative scoring method to the expression of CEA, MIB-1 and p16

Objectives. To investigate whether combining a semi-quantitative scoring method with the immunohistochemical expression of CEA, MIB-1 and p 16, would improve the diagnostic accuracy of endocervical glandular lesions. Methods. The hematoxylin and eosin-stained sections of 95 cervical biopsies were examined by 4 different observers and were grouped into three categories, benign, dysplasia and adenocarcinoma in situ, depending on the degree of nuclear stratification, nuclear atypia and the number of mitosis and apoptotic figures. Each case was also stained immunohistochemically with antibodies against CEA, Ki-67 (MIB-1) and p16. Staining was graded as negative, weak and positive. The accuracy of the scoring method alone was compared to the accuracy of combining the score with the immunostaining results. Results. Using the semi-quantitative scoring system, most of the cases that were initially diagnosed as atypical hyperplasia or tuboendometrial metaplasia fell into the benign category. This scoring system discriminates effectively (Kruskal-Wall is, p < 0.001) between the three categories (benign, endocervical glandular dysplasia and adenocarcinoma in situ). When analyzing the immunohistochemical score, only Ki-67 staining seems to be effective mostly in discriminating between normal glands or glands with atypical hyperplasia and epithelial glandular dysplasia. Ki-67, CEA and p16 failed to discriminate between tuboendometrial metaplasia and epithelial glandular dysplasia. Combining the semi-quantitative scoring system with the immunohistochemical results discriminates between the three categories equally well as the semi-quantitative scoring system alone (Kruskal-Wallis, p < 0.001). Nevertheless, the proportion of cases that were classified similarly to the prestudy diagnosis was higher when the combined score was used. Conclusions. Combining a semi-quantitative scoring scheme with the immunohistochemical expression of CEA, MIB-1 and p16seems to be of value in classifying some endocervical glandular lesions. (c) 2006 Elsevier Inc. All rights reserved

Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly

Background. Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods. We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results. Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): -1.53 (-2.80, -0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion. The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment. © 2022 George Kontogeorgos et al

Multiple endocrine neoplasia type 2A syndrome presenting with corneal nerve thickening

Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

Structure-function correlations of growth hormone or/and prolactin-producing pituitary adenomas: An in vitro study with the reverse hemolytic plaque assay

The purpose of this study was to detect in vitro growth hormone (GH) and prolactin (PRL) secretion from adenomas clinically associated with GH or PRL hypersecretion. The reverse hemolytic plaque assay (RHPA) was applied in order to reveal possible differences among various morphologic adenoma types, and to examine the inhibitory effects of octreotide on GH release as well. The 20 surgically resected pituitary adenomas studied included 15 from acromegalic patients and 5 from patients with hyperprolactinemia. All adenomas were diagnosed by histology, immunocytochemistry and electron microscopy. Among tumors associated with acromegaly, 5 were densely granulated (DG), 5 were sparsely granulated (SG) somatotroph (SM) adenomas, 2 were mammosomatotroph (MSM) and 3 mixed somatotroph-lactotroph cell (mixed SM-LT) adenomas; tumors causing hyperprolactinemia included 4 lactotroph (LT) adenomas and 1 mixed SM-LT adenoma. GH release assessed by the RHPA corresponded to in vivo hormone secretion and to tissue immunoreactivity. Statistical analysis showed significant differences among all morphologic types of SM adenomas, exclusive of SG-SM adenomas compared to mixed SM-LT adenomas. The mean plaque size in DG-SM and MSM adenomas was significantly greater than that of SG-SM and mixed SM-LT adenomas, indicating higher GH secretion by the former two types during the same incubation time. PRL secretion was documented in 2 mixed SM-LT adenomas. Plaques for PRL, but not for GH were formed in all LT adenomas. In all SM and LT adenomas, cells producing large plaques represented a minority of the plaque-forming cell population, however, they accounted for the largest part of the total plaque area, thus the largest part of hormone secretion. Octreotide effects on GH release were studied in 6 adenomas by the RHPA. Octreotide treatment induced a rapid and significant reduction in GH secretion by SM cells in vitro, with a selective effect on high-secreting cells