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- Alpy, F, et al.
(författare)
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The expression pattern of laminin isoforms in Hirschsprung disease reveals a distal peripheral nerve differentiation
- 2005
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 36:10, s. 1055-1065
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Tidskriftsartikel (refereegranskat)abstract
- Hirschsprung disease (HD), a developmental disorder, is associated with failure of enteric ganglia formation. Signaling molecules, including secreted basement membrane molecules, derived from the mesenchyme of the gut wall play an important role in the colonization and/or differentiation of the enteric nervous system. The current study aims to define the possible alterations of laminins involved in the pathogenesis of HD. Expression of the various laminin alpha, beta, and gamma chains, was assessed in the aganglionic, transitional, and ganglionic bowel segments of patients with HD or with other motor disorders. Cytoskeletal, neuronal, and glial markers were also included in this study. The major finding highlighted by the present work concerns the clear identification and location of myenteric aganglionic plexuses in HD with some of the laminin antibodies, which reveal a peripheral nerve type of differentiation. Furthermore, we could show an increase of laminin alpha 5 chain immunostaining in the dilated muscle of the ganglionic bowel upstream the distal aganglionic region in a subgroup of patients with HD, as well as a relocalization of laminin alpha 2 chain in the subepithelial basement membrane. Overall, these basement membrane molecules could provide useful markers for diagnosis of aganglionosis or hypoganglionosis.
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- Bernardo, Carina, et al.
(författare)
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Molecular pathology of the non-luminal Ba/Sq-like and Sc/NE-like classes of urothelial tumours : An integrated immunohistochemical analysis
- 2022
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177. ; 122, s. 11-24
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Tidskriftsartikel (refereegranskat)abstract
- Several groups have during past years produced molecular classification schemes for bladder cancer. Even though no consensus on how to define a subtype exists, one approach has been to base definitions on how tumours cluster according to their mRNA expression profiles. In many cases, obtained profiles, and thus class defining features, are affected by signals from non-tumour cells within the biopsy. To overcome this issue, we combined gene expression analyses with analyses of the actual tumour cells by extensive immunohistochemistry (IHC). By this approach we were able to define tumour cell phenotypes i.e., subtypes defined by features of the tumour cells only, and adjust mRNA-based algorithms accordingly. In the present investigation we address the non-luminal Basal/Squamous-like (Ba/Sq) and Small cell/Neuroendocrine-like (Sc/NE) categories of tumours defined by mRNA-based classification. We make use of IHC data for 15 proteins, all known to be instrumental for defining molecular subtypes of urothelial carcinoma. We show that the UroB type of tumours, frequently grouped together with Ba/Sq, are different from the Ba/Sq entity at several essential features and is a derivative of Urothelial-like tumours (Uro). We show that the Sc/NE tumours are similar to but represents extreme versions of Genomically Unstable (GU) tumours. We apply clustering to 423 cases representing all subtypes using IHC data for 14 proteins and show that the obtained grouping conforms well with the mRNA-based classification. This work describes in detail the molecular pathology of non-luminal RNA-based bladder cancer subtypes and highlight similarities/dissimilarities suggestive of origin.
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- Boström, Anna-Karin, et al.
(författare)
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Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
- 2012
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 43, s. 708-719
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.
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