Browsing by Subject "Ki-67"

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    Grading lung neuroendocrine tumors: Controversies in search of a solution
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Pelosi, Giuseppe; Pattini, Linda; Morana, Giovanni; Fabbri, Alessandra; Faccinetto, Alex; Fazio, Nicola; Valeri, Barbara; Sonzogni, Angelica
    Background. Pathological grading of tumors is a way to measure biological aggressiveness. In lung neuroendocrine tumors (NET), grading is tautologically included into the current 2015 WHO histologic classification. Little is known, however, about alternative grading systems in lung NET. Methods. Through an extensive search of the English literature on lung NET (updated to April 2016), the following key questions were addressed: a) current concepts of grading; b) clinicians’ requests for grading; c) functional parameters for grading; d) Ki-67 labeling index (LI) for grading; e) towards an effective pathology grading system. Results. There is some room for inconsistency in the histologic classification of lung NET, likely due to the varying attribution of defining criteria. Innovative diffusion-weighted imaging upon magnetic resonance or molecular analysis could help separate indolent from aggressive lung NET, thus integrating a grading approach other than histology. Troubles in the clinical handling of metastatic or individual tumors when relying on morphology alone support the development of a lungspecific grading system for the more accurate prediction of prognosis and planning therapy in individual patients. To integrate the 2015 WHO classification using innovative grading based on Ki-67 LI, mitotic count and necrosis, a new proposal is emerging where three categories of lung NET are identified, namely Lu-NET G1, Lu-NET G2 and Lu-NET G3, which would allow tumors with similar behavior and therapy to be better handled according to their own biological potential. Conclusion. A new formulation of lung NET grading could have clinical relevance for the individual handling of patients. Key words:
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    Immunohistochemical expression and localization of MMP-9, MMP-13, E-Cadherin and Ki-67 in road pavers' skin chronically exposed to bitumen products.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Loreto, Carla; Lombardo, Claudia; Caltabiano, Rosario; Filetti, Vera; Vitale, Ermanno; Seminara, Danilo; Castorina, Sergio; Fenga, Concettina; Ledda, Caterina; Rapisarda, Venerando
    To investigate the matrix metalloproteinase (MMP)-9, (MMP)-13, E-Cadherin and Ki-67 expressions in road pavers’ skin chronically exposed to bitumen products in order to contribute to a better understanding of the earlier tissue alteration. Skin punch biopsies from 16 daily exposed workers and a control group were studied by immunohistochemistry. Morphometric and densitometric analyses were also conducted. Morphological specimen evaluation of skin of road pavers showed epidermal thinning, flattening and loss of intercellular junction with a decreased expression of E-cadherin confined to the basal skin layer, together with MMP-9 and MMP-13 overexpressions in all epidermis layers, vascular structures and adnexa. No immunohistochemical alteration was reported for Ki-67 vs normal skin. Results from this study show that overexpression of MMP-9 and MMP-13 may represent an early response of the first human barrier to exposure to bitumen products. Regulation of MMPs could be one of the strategies to prevent primary skin disease.
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    Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.
    (Celular e Histiologia Universidad de Murcia, Departamento de Biologia, 2019) Zhu, Wang-Yu; Hu, Xiao-Fei; Fang, Ke-Xin; Kong, Qiong-Qiong; Cui, Ri; Feng, Hai; He, Jian-Ying; Zhang, Yong-kui; Le, Han-Bo
    Introduction. The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. Material and methods. Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. Results. Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and <0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF- 1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). Conclusion. The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.
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    SPHK2 protein expression, Ki-67 index and infiltration of tumor-associated macrophages (TAMs) in human glioma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Liu, J.; Zhou, Q.; Wu, C.P.; Xu, Y.W.; Liu, W.L.; Zhao, H.F.; Li, W.P.
    Introduction. Sphingosine kinases (SPHKs), the Ki-67 index and tumor-associated macrophages (TAMs) are associated with diverse human malignancies, including glioma. SPHK2, a subtype of SPHKs, has not been assessed in glioma or correlated with the Ki-67 index or TAM infiltration. We tested the hypothesis that expression of SPHK2 correlates with the Ki-67 index and TAM infiltration in patients with glioma. Materials and method. Western blot analysis was performed on protein lysates prepared from human astrocyte (HA) and glioma cell lines. Immunofluorescence was used to determine the subcellular location of SPHK2 protein in glioma cells. Next, immunohistochemistry was employed to analyze the correlations among SPHK2, Ki-67, CD68, and CD206 in 11 non-neoplastic brain tissues and 60 glioma tissues. All slides were evaluated under ×400 magnification, and the ratio of positively stained cells to the total number of cells was calculated for analysis. Results. SPHK2, CD68 and CD206 were all increased in glioma tissues compared to non-neoplastic brain tissues, but there were no differences between WHO grades of glioma. Ki-67 was highest in WHO grade IV tumors and lowest in non-neoplastic brain tissues, and all between-group differences were statistically significant. Moreover, SPHK2 expression was positively correlated with the Ki-67, CD68 and CD206 indexes. Finally, the CD68 and CD206 indexes were both associated with the Ki-67 index. Conclusion. SPHK2 protein expression, the Ki-67 index and TAM infiltration in human glioma tissue were reported in this study for the first time. SPHK2 was positively associated with TAM infiltration and glioma proliferation. Mechanistically, SPHK2 may promote glioma growth by stimulating TAMs to polarize M2-type macrophages.