Female Sex Hormone Receptors in Gallbladder Cancer

Bharathi, Ramanathan Saranga; Singh, Rajinder; Gupta, Rajesh; Verma, Geetika; Kalra, Naveen; Kiran, Kajal; Joshi, Kusum

doi:10.1007/s12029-015-9698-z

Cited by 18 publications

(9 citation statements)

References 16 publications

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“…This study also suggested that ER and PR may act as potential anti-hormonal therapy for gallbladder cancer. Bharathi et al [29] also aimed to check the ER and PR expression in 47 cases of GBC through the IHC method, and observed that both were simultaneously expressed in a significant proportion (23.4%) of GBC patients. This study further found out that receptor expression correlated with metaplasia, dysplasia, and the early stage of a tumor, whereas nonexpression of the receptor correlated with the metastatic stage.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions

et al. 2023

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Chronic inflammation in the gallbladder leading to persistent epithelium damage promotes invasive cancer. The study aimed to assess the prognostic value of PDL1 and CA19-9 markers in cancer/inflammatory lesions of the gallbladder. A total of 29 cases (19 cancer and 10 inflammatory) were included. The PDL1 protein concentration level and mRNA expression were assessed in the tissues’ lysates by ELISA and real-time PCR, respectively. PDL1 and CA19-9 concentration levels were compared and statistically related with clinico-pathological variables. The PDL1 protein level and its relative mRNA expression were correlated. Kaplan–Meir survival and Cox regression analyses were conducted for predicting prognosis. This study investigated the PDL1 and CA19-9 marker expression in both cancer and inflammatory cases of the gallbladder (p=0.48 and p=0.17 respectively). PDL1 protein expression was significantly associated with the hormonal profile of the cases (p=0.04) at an optimum cut-off value of 13pg/mL, while the CA19-9 marker expression was correlated with the status of liver metastasis (p=0.0043) and size of the tumor (p=0.004). A low PDL1 concentration was found when compared to the CA19-9 level among cancer cases (p=0.12) and proportional in the inflammatory lesions (p=0.63). A significant positive correlation was found between the PDL1 protein and its relative mRNA expressions in the inflammatory lesions (p=0.029) when compared to cancer cases (p=0.069). Our results showed that a protein-based assay for PDL1 expression would be more sensitive compared to RNA based assays for GBC risk stratifications. Overall survival was predicted with CA19-9 and PDL1 levels (p=0.0074, p=0.23, respectively). PDL1 and CA19-9 may act as a probable predictor of a poor prognosis in gallbladder cancer (GBC) cases.

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Section: Discussionmentioning

confidence: 99%

Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions

et al. 2023

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“…High levels of endogenous oestrogen and acquisition of exogenous oestrogen are all shown to exert a critical role on the incidence and prognosis of GBC . While ER signalling seems to be vital for gallbladder cancer, attention has not been paid to the current clinical treatment . TAM is a classical oestrogen receptor antagonist widely used in the treatment of breast cancer, while roles of TAM in GBC are still lacking (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…10,34,35 While ER signalling seems to be vital for gallbladder cancer, attention has not been paid to the current clinical treatment. 36 TAM is a classical oestrogen receptor antagonist widely used in the treatment of breast cancer, 11,37 while roles of TAM in GBC are still lacking (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Huang

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females two-threefold higher than males, suggesting oestrogen/oestrogen receptors (ERs) signalling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Quantitative real-time PCR was used to investigate mRNA levels. Protein expression was measured by immunohistochemistry and Western blot. Glycolytic levels were measured by glucose consumption and lactic acid measurement. The antitumour activity of TAM alone or with cisplatin was examined with CCK8 assay, colony formation, flow cytometry and in vivo models. The results revealed that ERɑ expression was higher in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor Nrf2 expression and its target genes, leading to the activation of AMPK, which subsequently induced impaired glycolysis and survival advantages. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of oestrogens by ovariectomy in nude mice prevented CDDP resistance. In summary, these results provide basis for TAM treatment for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC.

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“…Data on PR immunostaining in the literature typically lacks associations with patient age, gender, or stage in cancer [ 6 – 14 ] and is overall highly variable. For example, the reported range of PR positivity ranges from 0 to 76% in colorectal cancer [ 6 – 8 ], from 0 to 52% in adenocarcinoma of the gall bladder [ 9 , 10 , 15 , 16 ], from 0 to 85% in prostate cancer [ 11 , 17 , 18 ], from 0 to 63% in non-small-cell lung cancer [ 12 , 19 , 20 ], from 38.7 to 75.8% in papillary thyroid carcinoma [ 13 , 14 , 21 – 24 ], and from 15.2 to 100% in angiomyolipoma of the kidney [ 25 – 27 ]. These conflicting data are likely to be caused by the use of different antibodies, staining protocols, and interpretation criteria in these studies.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors

Viehweger

Tinger

Dum

et al. 2022

Analytical Cellular Pathology

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Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor family of ligand-dependent transcription factors. It plays an important role in reproduction and mammary gland development and has various tissue-specific effects in nonreproductive organs. In diagnostic pathology, positive PR immunostaining is used to support a diagnosis of breast or gynecologic origin in a tumor. In this study, the expression of PR was analyzed by immunohistochemistry in 18,176 (interpretable: 16,445) samples from 147 different tumor types and subtypes in a tissue microarray format. PR immunostaining was detected in 57.4% of breast tumors, 28.6% of other gynecological tumors, and 1.8% of nongynecological and nonmammary tumors. Among the group of nongynecological and nonmammary tumors, particularly high rates of PR positivity were seen in neuroendocrine tumors (54.3%) and neuroendocrine carcinomas (35.7%) of the pancreas. A comparison with clinico-pathological parameters showed that reduced PR immunostaining was significantly associated with adverse histopathological and clinical features in breast carcinoma, endometrioid endometrial carcinoma, and pancreatic neuroendocrine tumors. In summary, our analysis of 147 different tumor types for PR immunostaining provides a ranking list of tumor entities according to their prevalence of PR positivity, helps to better understand the diagnostic utility of PR, and highlights the distinct PR positivity among neuroendocrine neoplasms of pancreatic origin.

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Female Sex Hormone Receptors in Gallbladder Cancer

Cited by 18 publications

References 16 publications

Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions

Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors

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