Expression of HNF-1β in cervical carcinomas: an immunohistochemical study of 155 cases

Němejcová, Kristýna; Cibula, David; Dundr, Pavel

doi:10.1186/s13000-015-0245-9

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…The difference of HNF-1β expression between cervical SCC and adenocarcinoma was statistically significant (p < 0.001). This is close to study by Němejcová et al [13].…”

Section: Discussionsupporting

confidence: 74%

“…We assessed and graded the stained slides based on the percentage of stained cells as; one = 5-30 percent; two = 31-60 percent; three > 60 percent & zero < 5 percent of positive cells, the intensity of HNF-1β stain as weak one, moderate two or strong three [13]. We calculate the total final from zero to nine by multiplying the intensity values by the percentages of positive cells; we consider the final cut-off point is four above which considered high-expression and below which was considered low-expression of the marker.…”

Section: Evaluation Of Hnf-1β Protein Expressionmentioning

confidence: 99%

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Combined expression of ALEX1 and HNF-1beta could improve the ability of differentiation between squamous cell carcinoma and adenocarcinoma of the uterine cervix

Atwa¹,

Mohamed²

2018

Am J Res Med Sci

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Objective: Differentiation between poorly differentiated cervical squamous cell carcinoma (SCC) & adenocarcinoma which is essential for proper therapy, by histopathology alone can be confusing. Immunohistochemistry can aid important data to diagnosis. The transcription factor hepatocyte-nuclear-factor-1-beta (HNF-1β) essentially participates in the visceral-endoderm differentiation from the primitive-endoderm. Arm-protein-lost-in-epithelial-cancers-on-chromosome X (ALEX) is a recent subtype of armadillo-families that had arm-repeat-domains, detected on chromosome-X. The goal of our research: was to explore the diagnostic roles of HNF-β and ALEX-1 protein expressions, in differentiation between adenocarcinoma and squamous-cell-carcinoma of the cervix using immunehistochemical method. Methods: HNF-1-β and ALEX-1 protein expressions were evaluated in 32 cases of SCC and 18 cases of adenocarcinoma of the cervix. The relationships between their levels of expression and the ability of panel of both markers in differentiation between both types of carcinomas were analyzed. Results: We observed positive staining for HNF-1β in 83.4% (15/18) of adenocarcinoma cases. The difference of HNF-1β expression between cervical SCC and adenocarcinoma was statistically significant (p < 0.001). Positive ALEX-1 expression was observed in all cases of SCC of the cervix. The difference of ALEX-1expression between cervical SCC and adenocarcinoma was statistically significant (p < 0.001). This methodology for distinguishing cervical squamous cell carcinoma and adenocarcinoma had a sensitivity of 93.8% and a specificity of 100% (p < 0.001). Conclusion:The panel of both HNF-1β and ALEX-1 expressions can help in proper subtyping of cervical carcinoma with high sensitivity and specificity. ARTICLE HISTORY

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“…The difference of HNF-1β expression between cervical SCC and adenocarcinoma was statistically significant (p < 0.001). This is close to study by Němejcová et al [13].…”

Section: Discussionsupporting

confidence: 74%

Section: Evaluation Of Hnf-1β Protein Expressionmentioning

confidence: 99%

Combined expression of ALEX1 and HNF-1beta could improve the ability of differentiation between squamous cell carcinoma and adenocarcinoma of the uterine cervix

Atwa¹,

Mohamed²

2018

Am J Res Med Sci

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“…In the current study, HNF1β was positive in 13 of 14 (93%) tumours tested and although immunoreactivity was weak in a number of cases, it was almost always diffuse. In another study, 42 of 56 (75%) cervical adenocarcinomas exhibited positive nuclear staining with HNF1 β but the morphological subtypes were not detailed (31). Given that some clear cell carcinomas are only weakly positive with HNF1β, this marker is of no value in distinguishing gastric-type adenocarcinoma from clear cell carcinoma.…”

Section: Discussionmentioning

confidence: 97%

A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas

Carleton

Hoang

Sah

et al. 2016

American Journal of Surgical Pathology

138

156

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Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV) related cervical adenocarcinoma. They comprise a spectrum from a well differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumours have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphological overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, non-gynaecological sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were CK7, CK20, CDX2, CEA, CA125, CA19.9, p16, ER, PR, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta (HNF1β), carbonic anhydrase IX (CAIX), HER2 and MMR proteins. All markers were classified as negative, focal (<50% of tumour cells positive) or diffuse (≥50% tumour cells positive) except for p53 (classified as “wild-type” or “mutation-type”), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas) and MMR proteins (categorised as retained or lost). There was positive staining with CK7 (47/47 – 45 diffuse, 2 focal), MUC6 (17/21 – 6 diffuse, 11 focal), CEA (25/31 – 12 diffuse, 13 focal), CAIX (20/24 – 8 diffuse, 12 focal), PAX8 (32/47 – 20 diffuse, 12 focal), CA125 (36/45 – 5 diffuse, 31 focal), CA19.9 (11/11 – 8 diffuse, 3 focal), HNF1β (13/14 – 12 diffuse, 1 focal), CDX2 (24/47 – 4 diffuse, 20 focal), CK20 (23/47 – 6 diffuse, 17 focal) and p16 (18/47 – 4 diffuse, 14 focal). Most cases were negative with ER (29/31), PR (10/11), PAX2 (18/19) and HER2 (25/26). p53 showed “wild-type” and ”mutation-type” staining in 27/46 and 19/46 cases respectively. MMR protein expression was retained in 19/20 cases with loss of MSH6 staining in one patient with Lynch syndrome. Molecular studies for HPV were undertaken in two tumours which exhibited diffuse” block-type” immunoreactivity with p16 and both were negative. This is the first detailed immunohistochemical study of a large series of gastric-type adenocarcinomas of the lower female genital tract. Our results indicate immunophenotypic overlap with pancreaticobiliary adenocarcinomas but suggest that PAX8 immunoreactivity may be especially useful in distinguishing gastric-type adenocarcinomas from pancreaticobiliary and other non-gynaecological adenocarcinomas which are usually negative. Diffuse “block-type”p16 immunoreactivity ...

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“…In tumors, mutations and epigenetic inactivation of the HNF-1β gene has been shown to be involved in the development of several cancers [15–17]. Recently, it has been reported that the expression of HNF-1β in cervical carcinoma is mostly restricted to adenocarcinomas and can be used as an auxiliary adenocarcinoma marker in the differential diagnosis of poorly differentiated cervical carcinomas [18]. However, the expression and precise role of HNF-1α (HNF1A) in carcinogenesis as well as the importance of molecular targeting of this protein for therapeutic purposes remains unknown.…”

Section: Introductionmentioning

confidence: 99%

DNMT1 recruited by EZH2-mediated silencing of miR-484 contributes to the malignancy of cervical cancer cells through MMP14 and HNF1A

Liu

et al. 2019

Clin Epigenet

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BackgroundEmerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to cervical cancer (CC) tumorigenesis and development. Previous work showed that miR-484 which regulated the EMT process was obviously downregulated in CC. However, little is known about the precise mechanism.ResultsWe found that the deficiency of EZH2-recruited DNA methyltransferases DNMT1 reduced the CpG methylation of miR-484 promoter and then increased the miR-484 expression. Furthermore, the cell membrane-bound matrix metalloproteinase (MMP14) and the hepatocyte nuclear factor 1A (HNF1A) were found to be downregulated by miR-484. miR-484 repressed the expression of MMP14 and HNF1A inhibiting CC growth and metastasis in vitro and in vivo. Upregulation of MMP14 and HNF1A promotes the CC cell adhesion and EMT, all of which contribute to cell motility and metastasis. Moreover, miR-484 negatively regulates the WNT/MAPK and TNF signaling pathway by downregulating HNF1A and MMP14 respectively. Thus, miR-484, who is downregulated by DNMT1-mediated hypermethylation in its promoter, functions as a tumor suppressor by inhibiting MMP14 and HNF1A expression in CC.ConclusionOur finding characterizes miR-484 as a key suppressive regulator in CC metastasis and reveals a DNMT1-mediated epigenetic mechanism for miR-484 silencing, expanding our understanding of the molecular mechanism underlying CC progression and metastasis.Graphical abstract

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Expression of HNF-1β in cervical carcinomas: an immunohistochemical study of 155 cases

Cited by 13 publications

References 27 publications

Combined expression of ALEX1 and HNF-1beta could improve the ability of differentiation between squamous cell carcinoma and adenocarcinoma of the uterine cervix

Combined expression of ALEX1 and HNF-1beta could improve the ability of differentiation between squamous cell carcinoma and adenocarcinoma of the uterine cervix

A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas

DNMT1 recruited by EZH2-mediated silencing of miR-484 contributes to the malignancy of cervical cancer cells through MMP14 and HNF1A

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