The Pattern of p14<sup>ARF</sup> Expression in Primary and Metastatic Human Endometrial Carcinomas

Olcha, Piotr; Cybulski, Marek; Skomra, Danuta; Obrzut, Bogdan; Ignatov, Atanas; Jóźwik, Maciej; Schneider‐Stock, Regine; Semczuk, Andrzej

doi:10.1111/igc.0b013e3181e76a4d

Cited by 4 publications

(6 citation statements)

References 22 publications

(27 reference statements)

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“…In general, p14 ARF increases MDM and p21 levels and leads to cell cycle arrest in G1 and G2/M phases of the cell cycle [111,112,113]. Data concerning the role of alterations in p14 ARF in primary ECs and CSs are strictly limited [114,115,116,117,118,119,120]. A mini-review article concerning the role of p14 ARF alterations during endometrial tumorigenesis has recently been published [114].…”

Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

“…A mini-review article concerning the role of p14 ARF alterations during endometrial tumorigenesis has recently been published [114]. More than half of the primary human ECs and corresponding metastatic lesions displayed a p14 ARF expression pattern [119]. Interestingly, protein immunoreactivity was significantly related to transtubal tumor dissemination [119].…”

Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

“…More than half of the primary human ECs and corresponding metastatic lesions displayed a p14 ARF expression pattern [119]. Interestingly, protein immunoreactivity was significantly related to transtubal tumor dissemination [119]. Unpublished data revealed p14 ARF overexpression in 4 of 10 uterine CSs in both tumor components [Semczuk et al, pers.…”

Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

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Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

et al. 2014

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Carcinosarcomas (CSs; malignant mixed Müllerian tumors) of the uterus are highly malignant neoplasms characterized by an unfavorable outcome. They represent less than 5% of all uterine malignancies, and the median patient survival rate is only 21 months. p53 pathway alterations have been studied in CSs originating from the uterus, supporting the monoclonal nature of most but not all of these neoplasms. This paper gives an overview of the current knowledge of p53 pathway distortions in patients with uterine CSs. The survival of patients with uterine CSs in relation to p53 pathway alterations is also briefly summarized.

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Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

Section: P14arf Alterations/overexpression In Uterine Cssmentioning

confidence: 99%

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Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

et al. 2014

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“…Certain modulations in EC cells kinetics, possible via alterations in this pathway, [p14ARF/p53/p21(WAF1)], may result from a correlation between Sox9 and NF-ĸB signalling mechanisms, as well as from the Akt status (26). Olcha et al have observed expression of p14ARF protein in more than a half of the analyzed primary EC and metastatic lesions and found it to be positively associated with the transtubal dissemination of the primary tumour (27). Expression of p14ARF has been found by Watanabe et al to be significantly higher in G1 EC tumours than in normal endometrial hyperplasias (5).…”

Section: Discussionmentioning

confidence: 99%

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Wujcicka¹,

Zając²,

Szyłło³

et al. 2020

In Vivo

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Background/Aim: This research was aimed to evaluate the association between three selected single nucleotide polymorphisms (SNPs) within the CDKN2A (P14ARF) tumour suppressor gene and the incidence of endometrial cancer (EC) in postmenopausal women. Patients and Methods: The study included 194 postmenopausal women; 144 with EC and 50 noncancer controls. Genotypes in P14ARF rs3088440, rs3731217 and rs3731245 polymorphisms were assayed using PCR-RFLP and confirmed by sequencing. Results: Regarding the rs3088440 polymorphism, CT, and CT-TT genotypes, were more prevalent among EC patients than in controls (OR=5.55, p=0.023, OR=5.29, p=0.027; and OR=2.92, p=0.023, respectively). The T allele within rs3088440 was more prevalent in EC females than in controls (χ 2 =4.7, p=0.030). Considering rs3731217, TG and TG-GG genotypes were less prevalent among EC (OR=0.34, p=0.024 or p=0.023; and OR=0.38, p=0.035, respectively). Conclusion: Polymorphisms in the CDKN2A gene are associated with EC in postmenopausal women. Endometrial cancer (EC) is the fourth most common cancer among Polish women (after breast, colon, and lung cancer) responsible for 3% of cancer deaths in this population. Moreover, the incidence rate of this cancer has almost doubled in the last three decades, due to several factors, especially the increased average life expectancy of women. Hence, EC is predominantly observed in postmenopausal women in their sixth/seventh decade of life, with the highest incidence rate of 80/100,000 at the end of the seventh decade (1). P14ARF belongs to three tumour suppressor proteins, including p16INK4a and p15INK4b encoded by the CDKN2A gene, genetic changes of which may cause cellular proliferation and tumour growth (2, 3). It has been shown that p14ARF influenced the course of cell cycle by activating p53 and inhibiting MDM2 expression thus leading to cell cycle arrest in G 1 and G 2 /M phases (4, 5). Altered expression of p14ARF, either decreased or increased, has been found in various human tumours (5-8). Considering EC, tumor heterogeneity in CDKN2A protein expression between four different cores of primary tumours, has been reported as significantly more prevalent among samples with a higher stage of the disease (9). In another study, CDKN2A tumour suppressor gene was included in a panel of seven immunohistochemical markers [ER, CDKN2A (p16), TP53, VIM, PTEN, PGR, and IGF2BP3] to differentiate endometrioid carcinoma in FIGO grade 3 from serous carcinoma, based on immunohistochemical qualitative assays performed by tissue microarrays (10). Moreover, moderate immunohistochemical expression of p14 has been observed in endometrioid endometrial carcinoma, while total lack has been found in endometrial hyperplasias without atypia, at the 943 This article is freely accessible online.

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“…Similarly, in Polish postmenopausal women, MDM2 SNP 309 GG and TP53 rs1042522 Arg-Arg genotypes, as well as the combined GG and Arg-Arg variants, have been reported to be associated with increased risk of EC (9)(10)(11). So far, alterations in p14ARF-MDM2-p53 tumor suppressor pathway have been reported to be associated with tumorigenesis of different cancers, including EC (12,13). High expression of p53 accompanied by low levels of MDM2 and p14ARF, have been shown to be possibly correlated with low differentiated primary EC (14).…”

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confidence: 93%

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

Wujcicka¹,

Zając²,

Stachowiak³

2019

In Vivo

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Background/Aim: The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women. Materials and Methods: The study group consisted of 144 EC women and 50 non-cancer controls. MDM2 rs22279744, TP53 rs1042522, and P14ARF rs3088440, rs3731217, and rs3731245 SNPs were analysed.

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The Pattern of p14^ARF Expression in Primary and Metastatic Human Endometrial Carcinomas

Cited by 4 publications

References 22 publications

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

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The Pattern of p14ARF Expression in Primary and Metastatic Human Endometrial Carcinomas

Cited by 4 publications

References 22 publications

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

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The Pattern of p14^ARF Expression in Primary and Metastatic Human Endometrial Carcinomas