Background: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. Methods: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. Results: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. Conclusion: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.

DNA/RNA‐based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high‐resolution proteomics analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype‐specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low‐risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross‐omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.

Simultaneous deregulation of caspase-8 and -3 is a frequent event in tongue squamous cell carcinoma. Activation of caspase-3, which is predominantly down-regulated, may be a crucial process for induction of apoptosis and response to therapeutic strategies.

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