Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm
HISTOPATHOLOGY
Authors: Nakaguro, Masato; Urano, Makoto; Ogawa, Ikuko; Hirai, Hideaki; Yamamoto, Yoshinari; Yamaguchi, Hiroshi; Tanigawa, Maki; Matsubayashi, Jun; Hirano, Hiroshi; Shibahara, Junji; Tada, Yuichiro; Tsuzuki, Toyonori; Okada, Yasuo; Sato, Yuichiro; Ikeda, Kenichiro; Sukeda, Aoi; Honda, Yumi; Mikami, Yoshiki; Nagao, Toshitaka
Abstract
Aims Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). Methods and results We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. Conclusion The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.
Altered expression of some miRNAs and their target genes following mesenchymal stem cell treatment in busulfan-induced azoospermic rats
GENE
Authors: Badawy, Abdelnaser A.; El-Magd, Mohammed A.; AlSadrah, Sana A.; Alruwaili, Mohammed M.
Abstract
Studies have recently demonstrated that mesenchymal stem cells (MSCs) have therapeutic capabilities on many diseases and this effect is mainly mediated by miRNAs. However, the actual mechanism of MSCs paracrine effect on testis to improve male fertility is still elusive. Herein, we evaluated the altered expression of some spermatogenesis-related miRNAs and their target genes following transplantation of bone marrow (BM)-derived MSCs into testes of busulfan-induced azoospermic rats using real time PCR. Transplantation of MSCs improved fertility of azoospermic rats as revealed by enhanced serum levels of testosterone and estradiol, and upregulated expression of germ cell-specific genes. Azo rats injected with MSCs also exhibited a significant downregulated expression of miRNA-19b, miRNA-100, miRNA-141, miRNA-146a, miRNA-429, and let-7a and a significant upregulated expression of miRNA-21, miRNA-34b, miRNA-34c, miRNA-122, miRNA-449a, miRNA-449b, and miRNA-449c in the testis as compared to Azo rats injected with phosphate buffer saline. Transplantation of MSCs was also accompanied with restoration of the disrupted expression of Ccndl, E2F1, Myc, and PLCXD3 (target genes for miRNA-34 and miRNA-449 clusters) and ERa and AKT1 (target genes for miRNA-100 and let-7a) to level comparable to that of the fertile group. Upon these data, we infer that BM-MSCs can improve fertility of azoospermic rats and this effect was followed by altered expression of some spermatogenesis-related miRNAs and their target genes. These findings provide MSCs as a promising and effective cell-based therapeutic method for azoospermic patients, but further investigations are required before clinical application.