KIT gene mutation and amplification in dysgerminoma of the ovary

BACKGROUND:

Dysgerminoma, the ovarian counterpart of seminoma, is the most common type of malignant ovarian germ cell tumor. The role of KIT mutation and amplification in the development of dysgerminoma is not currently established. The purpose of this study was to analyze alterations of the KIT gene in a large series of dysgerminomas and correlate the findings with clinicopathological parameters.

METHODS:

Dysgerminoma cells from 22 patients were analyzed for KIT mutations at exon 17 codon 816. KIT amplification and chromosome 12p anomalies were investigated by way of dual color fluorescence in situ hybridization. KIT protein expression was also examined by way of immunohistochemistry.

RESULTS:

KIT exon 17 codon 816 mutations and KIT amplification were each detected in 6 cases of dysgerminoma (27%); however, there was no correlation between these 2 factors. KIT expression was detected in 87% of dysgerminomas. The KIT mutation was associated with advanced pathological stage (P < .05), and KIT amplification was associated with elevated KIT protein expression (P < .05). Chromosome 12p anomalies were found in 82% of the dysgerminomas and did not correlate with KIT abnormalities.

CONCLUSIONS:

KIT mutations occur in approximately one‐third of cases of dysgerminomas and are associated with advanced stage at presentation. KIT is a potential therapeutic target for those dysgerminomas that have the mutation. Cancer 2011. © 2010 American Cancer Society.     

The development of cerebral connections during the first 20-45 weeks' gestation

We have correlated data on neuroanatomical organization and magnetic resonance imaging of transient fetal zones shown to contain connectivity elements (growing axons, synapses, dendrites). In the fetal phase, afferent fibres ‘wait’ within the subplate zone which is the most prominent lamina on histological and magnetic resonance images and is a substrate of endogenous neuronal activity. In early preterm the thalamocortical afferents accumulate within the superficial subplate and grow into cortical plate developing synapses. In late preterm, the resolution of the subplate and growth of cortico-cortical fibres into the cortical plate occur simultaneously with gyration. Both preterm phases characterize the coexistence of endogenous and sensory-driven circuitries and occurrence of the transient electrical phenomena. In neonates, the long cortico-cortical pathways stop growth, and the main histogenetic events are an elaboration of intracortical circuitry and synaptogenesis. In conclusion, the growth of the axonal pathways preterm explains their vulnerability and plasticity. In neonates the vulnerability is related to the intracortical circuitry.     

MUC gene expression and histogenesis of adenocarcinoma of the stomach.

To elucidate the histogenesis of adenocarcinomas of the stomach, we examined MUC gene expression in gland-forming intramucosal neoplastic lesions. Eighty tumors were histopathologically assigned to 1 of the following 3 groups based upon the Vienna classification: group A (low-grade adenoma/dysplasia), group B (high-grade adenoma/dysplasia) and group C (intramucosal carcinoma). Immunohistochemic staining was performed with monoclonal antibodies against MUC2 (goblet cell mucin), MUC5AC (gastric-foveolar mucin), MUC6 (pyloric-gland mucin) and CD10 (brush border). Ki-67 staining was also carried out. An obvious difference existed in MUC gene expression between lesions in group A and those in groups B and C. The majority of group A lesions strongly expressed intestinal markers in which proliferating cell zones were formed but generally expressed no gastric markers, whereas more than 50% of groups B and C tumors expressed gastric markers. These findings suggest that group A lesions are of a stable intestinal phenotype, whereas those in groups B and C are phenotypically and genotypically unstable, indicating that the adenoma-carcinoma sequence is not a major pathway, but instead that adenocarcinomas arise de novo.     

Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis,the degree of calcium oxalate deposition,histological type,and possible tumorigenesis

Enoki Y, Katoh G, Okabe H & Yanagisawa A
(2010) Histopathology 56, 384–394 Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis Aims: Acquired cystic disease of the kidney (ACDK) in patients undergoing haemodialysis is known to develop into renal cell carcinoma (RCC), but its pathogenesis remains unclear. The aims were to analyse the histological findings of ACDK‐RCC and to determine its histogenesis. Methods and results: Twenty‐nine RCCs in 23 patients with ACDK were classified into three groups according to the duration of haemodialysis and were analysed for histological type, calcium oxalate (Oxa) deposition, and cyst and atypical cyst (AC) formation. Histologically, 21 tumours were ACDK‐RCC and eight were clear cell carcinoma (CCC). The ratio of ACDK‐RCC and the numbers of cysts and ACs increased as the duration of haemodialysis was prolonged. The degrees of intratumoral Oxa deposition and cyst and AC formation of ACDK‐RCCs were higher than those of CCCs (Oxa, P = 0.028; cyst, P < 0.0001; AC, P = 0.0002). Many ACDK‐RCCs (85.7%) and some CCCs (50%) had characteristics of the thin ascending loop of Henle as assessed by CD57 (HNK‐1) expression, which was rarely expressed in the 29 control cases. Conclusions: ACDK‐RCCs reveal characteristics of Henle’s loop, which may be related to their peculiar pathological features, including intratumoral oxalate deposition and cyst and AC formation.     

Prichard's structures of the fossa ovalis are not histogenetically related to cardiac myxoma

AIMS: Cardiac myxomas are neoplasms of unknown histogenesis. They are thought to arise from hypothetical subendothelial vasoformative reserve cells or from primitive cells which reside in the fossa ovalis and surrounding endocardium. In 1951 Prichard described a kind of microscopic endocardial structure with a predilection for the interatrial septum, which were suggested to be related to cardiac myxomas. To confirm the existence of Prichard's structures and to clarify their role in the genesis of cardiac myxomas, we examined histologically the fossa ovalis and we performed an immunohistochemical study of the endocardial abnormalities that were found. METHODS AND RESULTS: A prospective histological study of 100 interatrial septa and an immunohistochemical study of three out of the 12 endocardial abnormalities that were detected, as well as of four conventional cardiac myxomas were accomplished. Antibodies were used to vimentin, CD31, CD34, alpha-smooth muscle actin, S100 protein, thrombomodulin, calretinin and c-kit (CD117), a tyrosine kinase growth factor receptor for stem cell factor usually expressed by embryonic/fetal endothelium. Structures similar to the ones described by Prichard were found in 12% of septa, most of them in the left side of the fossa ovalis. The hearts with these structures were from patients 10 years older than the ones without them (72 +/- 10 versus 62 +/- 16 years, P=0.006). Immunohistochemically the cells comprising Prichard's structures were positive for vimentin, CD31, CD34 and thrombomodulin, and negative for alpha-smooth muscle actin, S100 protein, calretinin and c-kit. Therefore these cells seem to be mature endothelial cells, but not primitive multipotential mesenchymal cells. Furthermore, these cells were not found in the atrial tissue from the bases of any of the conventional cardiac myxomas. CONCLUSIONS: Our study suggests that there is no apparent relation between Prichard's structures and cardiac myxomas, and that Prichard's minute endocardial deformities are age-related phenomena.     

Sebaceous carcinoma within rippled/carcinoid pattern sebaceoma

Although the histogenesis of sebaceous carcinomas remains unclear, the occurrence of intraepidermal or intraepithelial sebaceous carcinoma in the epidermis or conjunctiva may suggest de novo histogenesis. This report describes a case of sebaceous carcinoma within preexisting rippled/carcinoid pattern sebaceoma. This lesion was composed of two (benign and malignant) components, and the benign component of the lesion showed the typical features of a rippled/carcinoid pattern sebaceoma. Although evidence of trauma as well as a vertical orientation was seen in this lesion, the malignant component of the lesion showed histopathological evidence of malignancy (sebaceous carcinoma), such as the aggregations with irregular and infiltrated borders, a sheet‐like growth pattern, and the cytopathological findings of the neoplastic cells, showing a high‐grade of malignancy (a high mitotic index and abnormal mitotic figures). The immunohistochemical staining for p53, Ki‐67 and D2‐40 also favored this diagnosis. This sebaceous carcinoma component was considered to be the incipient stage of carcinoma within preexisting sebaceoma, therefore, it was still considered to be a vertically oriented lesion. This case shows the possibility that abnormal (malignant) sebaceous germinative cells may originate within a sebaceoma, thereby suggesting that some sebaceous carcinomas may develop from preexisting sebaceomas.     

Animal models of exocrine pancreatic carcinogenesis

In order to understand the evolution, histogenesis, and biological behaviour of exocrine pancreatic carcinoma, some reproducible experimental models have been developed in certain rodent species. To date, more than 16 chemicals, many of them structurally unrelated, have been shown to induce pancreatic tumors. Although some of these chemicals appear species specific in their effect on the pancreas, others have been shown to be capable of inducing pancreatic tumors in more than one species. In hamsters, the administration of diisopropylnitrosamine or its oxidized metabolites leads to the development of ductal adenocarcinomas that histologically resemble human pancreatic carcinomas. The histogenesis of the ductal type of adenocarcinoma in hamsters is complex, and appears to involve both the duct cells and dedifferentiated acinar cells. All pancreatic tumors in rats develop from acinar cells showing variable degrees of differentiation, regardless of the type of carcinogen used. The type of pancreatic lesions that develop in mice are also of acinar cell origin. In guinea pigs the tumors are adenocarcinomas of the ductal type and are shown to be derived from dedifferentiated acinar cells that have undergone duct-like transformation. Irrespective of the type of tumor that develops in these experimental animals, all of these models can be successfully used to evaluate the various modifying (risk) factors and biological behaviour of these neoplasms.     

Histogenesis of post-mastectomy angiosarcoma—an ultrastructural study

An example of post-mastectomy angiosarcoma was studied by electron microscopy to determine its histogenesis. Unequivocal evidence of endothelial differentiation was found in well and poorly differentiated areas. Positive staining for factor VIII related antigen and negative staining for epithelial membrane antigen further confirmed that the tumour was a true angiosarcoma rather than a peculiar form of carcinomatous metastasis.     

Expression patterns and cell cycle profiles of PCNA, MCM6, cyclin D1, cyclin A2, cyclin B1, and phosphorylated histone H3 in the developing mouse retina

A challenge in studying organogenesis is the ability to identify progenitor cell populations. To address this problem, we characterized the expression patterns of cell cycle proteins during mouse retinal development and used flow cytometry to determine the expression profiles in the cell cycle. We found that MCM6 and PCNA are expressed in essentially all retinal progenitor cells throughout the proliferative period and these proteins are readily detectable in all cell cycle phases. Furthermore, their expression levels are downregulated as cells exit the cell cycle and differentiate. We also analyzed the expression of Cyclins D1, A2, and B1, and phosphorylated Histone H3 and found unexpected expression patterns and cell cycle profiles. The combined utilization of the markers tested and the use of flow cytometry should further facilitate the study of stem and progenitor cell behavior during development and in adult tissues.     

小脑血管母细胞瘤的超微结构、免疫组织化学和细胞培养研究

目的:探讨小脑血管母细胞瘤(HB)的组织学起源。方法:对40例HBs作免疫组化染色,3例行电镜观察,10例行细胞培养。结果:HB中内皮细胞、周细胞、基质细胞成分都对Vimentin染色阳性,内皮细胞对CD34阳性,周细胞对SMA阳性,基质细胞对Telomerase阳性;基质细胞对VEGF染色阳性,而内皮细胞对Flt-1染色阳性。HB中的3种细胞成分各有其不同的超微结构特征,细胞培养显示不同HB标本中的基质细胞有一定的异质性。结论:HB可能来源于成血管间叶组织,基质细胞是HB中的肿瘤细胞,有一定的异质性。