Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the ...clinicopathological features of CK5‐positive ADC. We aimed to explore the clinicopathological characteristics of CK5‐positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5‐positive ADC was defined to have ≥ 10% tumour cells and presence of CK5‐positive tumour cells in the resected and TMA cohorts, respectively. CK5‐positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5‐positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high‐grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild‐type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5‐positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high‐grade components. In the TMA cohort, CK5‐positive ADCs correlated with TTF‐1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5‐positive ADCs had significantly lower disease‐free and overall survival rates than CK5‐negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5‐positive ADCs showed aggressive clinical behaviour, with high‐grade morphology and mucinous differentiation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
IntroductionThymic epithelial tumours (TETs) are the relatively rare tumours originated from thymus. TETs are histologically categorised according to the WHO classification based on the morphology of ...epithelial tumour cells and proportion of lymphocytic involvement. Epithelio-mesenchymal transition (EMT) has reported to play pivotal roles in tumour progression including invasion/metastasis, drug resistance, and cancer stemness. However, the precise clinicopathological associations with EMT characteristics in TETs remain to be elusive. Herein, we have examined EMT markers in TETs integrated with their clinicopathological information.Material and methodsA total of 109 patients with TETs were surgically resected between 2002 and 2017 in our institution. Tissue samples were collected from the paraffine-embedded tumour blocks of these patients. The 2 mm cores in diameter of the most representative areas of the tumours were selected by the pathologist and assembled to make tissue microarrays. Immunohistochemical (IHC) stainings for E-cadherin (E) and vimentin (V) were performed. P63 and pan-cytokeratin were additionally stained to detect epithelial tumour cells. The expressions of these molecules were scored and quantified to categorise the activation level of EMT into three groups based on the combination of E and V levels: Full; E-V+, Partial; E+V+ or E-V-. Null; E+V-. For statistical analyses, chi-square tests and Cox hazard models were applied. P-value less than 0.05 was considered significant.Results and discussionsThe median follow-up time was 54.3 months (range, 0.3–178.7). Predominant WHO histological subtypes were as follows: A;8, AB;18, B1;30, B2;30, B3;6. C;15, others;2. Pathologic stage distributions by TNM classfication were as follows: 1;80, 2;2, 3;13, 4a;7, 4b;4. The positive rates of E-cadherin or vimentin expression in epithelial tumour cells were 54.2% and 57.9%, respectively. EMT activation was significantly exhibited in indolent predominant WHO subtype, and in the early stage of pT factor and the Masaoka classification (p=0.0005, 0.0493, and 0.0366, respectively). Multivariate analyses of overall survival time including pT, pN, pM, age, and EMT levels showed that pT factor was significantly prognostic (p=0.0218), but not for EMT.ConclusionEMT activation mechanisms in TETs were inversely correlated with their histological subtype and the primary tumour progression. Further studies are necessary to elucidate tumour progression mechanisms in TETs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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