Absence of Human Papillomavirus Infection and Activation of PI3K-AKT Pathway in Cervical Clear Cell Carcinoma

Ueno, Sayaka; Sudo, Tamotsu; Oka, Noriko; Wakahashi, Senn; Yamaguchi, Satoshi; Fujiwara, Kiyoshi; Mikami, Yoshiki; Nishimura, Ryuichiro

doi:10.1097/igc.0b013e3182981bdc

Cited by 48 publications

(43 citation statements)

References 30 publications

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“…mTOR signaling pathway inhibitors might be a new therapeutic treatment in cervical cancer, 28 and SPAG5 expression in cervical cancer may be a potential indicator for mTOR inhibitor treatment.…”

Section: Discussionmentioning

confidence: 99%

SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

Yuan

Zhang

et al. 2014

Cell Death Dis

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Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in pelvic lymph node metastasis–positive cervical cancer. The aim of this study is to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical cancer and its clinical significance in tumor progression. In our study, SPAG5 expression in cervical cancer patients was detected using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry; cervical cancer cell function with downregulated SPAG5 in vitro was explored using tetrazolium assay, flow cytometry, and colony formation and Transwell assays. SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free survival, which was also an independent prognostic indicator for cervical cancer patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell proliferation and growth significantly by G2/M arrest and induction of apoptosis, and hindered cell migration and invasion. Under SPAG5 downregulation, the sensitivity of cervical cancer cells differed according to taxol dose, which correlated with mammalian target of rapamycin (mTOR) signaling pathway activity. In general, SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer.

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Section: Discussionmentioning

confidence: 99%

SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

Yuan

Zhang

et al. 2014

Cell Death Dis

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“…One study examining various molecular pathways by immunohistochemistry showed that a proportion of cervical CCCs had loss of PTEN, positivity for pAKT, and positivity for pmammalian target of rapamycin (mTOR) with 1 case showing human epidermal growth factor receptor 2 (HER2) amplification by fluorescence in situ hybridization. 67 However, no molecular analysis was performed in these cases and therefore, the correlation of these results with actual mutations is unknown.…”

Section: Clear Cell Carcinomamentioning

confidence: 98%

Cervical Adenocarcinomas: A Heterogeneous Group of Tumors With Variable Etiologies and Clinical Outcomes

Hodgson

Park

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Cervical adenocarcinomas are a heterogeneous group of tumors with varying morphologies, etiologies, molecular drivers, and prognoses, comprising approximately 25% of all cervical cancers. Unlike cervical squamous cell carcinoma, adenocarcinomas are not uniformly caused by high-risk human papillomavirus (HPV) infection and, therefore, would not necessarily be prevented by the HPV vaccine.Objective.-To provide a review of endocervical adenocarcinoma subtypes and, when appropriate, discuss precursor lesions, etiologies, molecular genetics, and ancillary studies within the context of clinical care. Some historical perspectives will also be provided.Data Sources.-Data sources included published peerreviewed literature and personal experiences of the senior author.Conclusions.-Endocervical adenocarcinomas are a histologically diverse group of tumors with various causes and molecular drivers, not all related to HPV infection. Distinguishing them has important implications for treatment and prognosis as well as strategies for prevention.

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“…Adenocarcinomas (including adenosquamous carcinomas) are the second most common histologic type linked to HPV infection, specifically usual-type endocervical, mucinous intestinal and villoglandular subtypes, followed by high-grade neuroendocrine carcinomas (HGNEC). Non-HPV-associated cervical carcinomas are rare, and predominantly comprise unusual adenocarcinoma variants: mesonephric adenocarcinoma, minimal deviation/gastric-type mucinous adenocarcinoma, and clear cell carcinoma (2, 3). …”

Section: Introductionmentioning

confidence: 99%

Mixed Mesonephric Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Uterine Cervix: Case Description of a Previously Unreported Entity With Insights Into Its Molecular Pathogenesis

Cavalcanti

Schultheis

et al. 2017

International Journal of Gynecological Pathology

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Human papillomavirus (HPV)-negative cervical carcinomas are uncommon and typically encompass unusual histologic subtypes. Mesonephric adenocarcinoma is one such subtype. Mesonephric tumors in the female genital tract are thought to arise from Wolffian remnants, and are extremely rare tumors with widely variable morphology. Sarcomatoid dedifferentiation has been previously described in a few cases, but other forms of dedifferentiation have not been reported. Neuroendocrine carcinoma of the cervix (e.g. small cell carcinoma) is associated with HPV infection, typically HPV 18. These tumors often arise in association with a conventional epithelial component such as squamous cell carcinoma or usual-type endocervical adenocarcinoma. We describe a case of mesonephric adenocarcinoma of the uterine cervix associated with an HPV-negative high-grade neuroendocrine carcinoma at the morphologic and immunophenotypic level, for which we performed targeted massively parallel sequencing analysis of the two elements. Both components shared identical mutations in U2AF1 p.R156H (c.467G>A) and GATA3 p.M422fs (c.1263dupG), as well as MYCN amplification. In addition, the neuroendocrine carcinoma harbored TP53 and MST1R mutations not present in the mesonephric carcinoma. Our data suggest a clonal origin of the two components of this rare entity, rather than a collision tumor.

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Absence of Human Papillomavirus Infection and Activation of PI3K-AKT Pathway in Cervical Clear Cell Carcinoma

Cited by 48 publications

References 30 publications

SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

SPAG5 upregulation predicts poor prognosis in cervical cancer patients and alters sensitivity to taxol treatment via the mTOR signaling pathway

Cervical Adenocarcinomas: A Heterogeneous Group of Tumors With Variable Etiologies and Clinical Outcomes

Mixed Mesonephric Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Uterine Cervix: Case Description of a Previously Unreported Entity With Insights Into Its Molecular Pathogenesis

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