Browsing by Subject "EGFR"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    Clinicopathological features and genomic analysis of bronchiolar adenoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Bo, Jiaqi; Chen, Xue; Zhang, TingTing; Zhu, Xuyou; Zhang, Long; Liu, Yuting; Zhang, Haoyang; Wu, Caixia; Mou, Shunyan; Yi, Xianghua; Rui, Weiwei; Zeng, Yu
    Background. Bronchiolar adenoma (BA) is a rare tumor of the bronchioles with a double-layer structure, including the basal cell layer and the superficial cell layer, and it has a good prognosis. However, the concept of a putative variant of BA has been proposed in the recent literature. Methods. Data on 17 cases of BA were collected from our center. The clinical data, morphology, immunophenotype, and molecular changes were retrospectively analyzed. We also collected the molecular changes in BA reported in the previous literature and summarized the putative driver mutations of BA. Results. Out of 17 BAs, 13 were classic cases with a double-layer structure, including 9 proximal-type and 4 distal-type BAs. Of note, we also identified 3 cases that lacked a continuous basal cell layer, including 2 cases of mixed-type BA with monolayered lesions (basal cells were undetected in some areas) and 1 case of a monolayered BA-like lesion (basal cells were completely undetected). The immunohistochemical findings of monolayer cell lesions were closer to those of minimally invasive adenocarcinoma. We also found one case in which BA transformed into invasive adenocarcinoma accompanied by mutations in the TP53, JAK2, NF1 and RB1 genes. Combined with the previous literature, the most common putative driver gene mutations in 62 BA lesions were EGFR (25/62; 41.0%) and BRAF (21/62; 34.4%). Conclusion. Typical BA has a double-layer cell structure; however, there is also a putative variant of BA, which has a monolayer cell structure and lacks the basal cell layer. Transformation from BA into invasive adenocarcinoma is unusual but can occur
  • Thumbnail Image
    Publication
    Open Access
    EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Martin, Vittoria; Zanellato, Elena; Franzetti-Pellanda, Alessandra; Molinari, Francesca; Movilia, Alessandra; Paganotti, Alessia; Deantonio, Letizia; De Dosso, Sara; Assi, Agnese; Crippa, Stefano; Boldorini, Renzo; Mazzucchelli, Luca; Saletti, Piercarlo; Frattini, Milo
    Background: Combined chemoradiation therapy is the gold standard in the treatment of squamous cell anal cancer (SCAC). However, even if the response rate is very high, many patients eventually relapse or experience a recurrence, thus requiring an invasive surgical procedure that has severe side effects. Most SCAC tumors overexpress epidermal growth factor receptor (EGFR); therefore, it is reasonable to consider anti-EGFR drugs as a new treatment option, as demonstrated by anecdotal reports. Promising results obtained in other solid tumors, both squamous and non-squamous, have revealed that an increase in the EGFR gene copy number may predict the efficacy of anti-EGFR therapies, while the presence of mutations in downstream members of the EGFR pathway may confer resistance. These markers have been only sporadically considered in SCAC. Methods: We investigated the status of the EGFR gene using FISH and examined KRAS, BRAF, and PIK3CA hot-spots mutations using sequencing analysis in a cohort of 84 patients affected by SCAC. Results: Twenty-eight patients (34%) showed an increase in EGFR gene copy number due to amplification (4%) or to polysomy (30%). KRAS and PIK3CA gene mutations were found in 4 (5%) and 13 patients (16%), respectively. No mutations were found in the BRAF gene. Conclusions: The characterization of the EGFR pathway may help in identifying different subgroups of SCAC that have specific molecular features, which may have implications in what targeted therapies are used to treat each patient. Histol Histopathol 29, 513-521 (2014)
  • Thumbnail Image
    Publication
    Open Access
    Inhibition of ubiquitin specific peptidase 8 is effective against 5-fluorouracil resistance in colon cancer via suppressing EGFR and EGFR-mediated signaling pathways
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Xi, Changlei; Gong, Zhilin; Ye, Hui; Cao, Longlei; Yu, Jie
    Background. The identification of a sensitizing strategy to overcome 5-fluorouracil (5-FU) therapeutic resistance is needed in colon cancer. Recent studies highlight the oncogenic role of ubiquitin specific peptidase 8 (USP8) in many cancers. In line with these efforts, this work investigated the therapeutic potential of targeting USP8 in colon cancer. Methods. Immunohistochemistry was performed to determine USP8 expression level in colon cancer tissues and their adjacent normal tissues. Gain-of-function analysis via plasmid overexpression and loss-of-function analysis via siRNA knockdown were applied on cellular assays. The combinatory effects of USP8 inhibitor and cisplatin were determined using a colon xenograft mouse model. Immunoblotting was performed to investigate the molecular mechanism of USP8 inhibition in colon cancer cells. Results. Compared to normal counterparts, we showed that USP8 protein level was significantly higher in colon cancer tissues and cells. In addition, USP8 expression was not affected by prolonged exposure of colon cancer cells to 5-FU. USP8 was important for colon cancer cell growth and survival but not migration as assessed by loss-of-function and gain-of-function approaches. Pharmacological inhibition of USP8 using USP8 inhibitor is active against both sensitive and 5-FUresistant colon cancer cells. Of note, USP8 inhibitor significantly inhibited colon cancer formation and growth, and augmented in vivo efficacy of 5-FU without causing toxicity in mice. Mechanistic studies showed that USP8 inhibitor acted on colon cancer cells through suppressing EGFR and EGFR-mediated signalling pathways. Conclusions. Our work is the first to reveal the essential role of USP8 in colon cancer via EGFR oncogenic signalling pathways. Our findings provide a proof-of-concept that USP8 inhibitors are promising candidates to overcome 5-FU resistance in colon cancer