P53 Expression in Adenomyosis in Endometrial Carcinoma Patients

Abstract.Lundgren C, Auer G, Frankendal B, Moberger B, Nilsson B, Nordström B. Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I–IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy (n = 340) and expression of MIB-1 (n = 318) and p53 (n = 323) were studied. In univariate analysis, stage (P < 0.001), histopathologic subtype (P < 0.001), degree of differentiation (P < 0.001), HRT (P = 0.034), DNA ploidy (P < 0.001), and p53 (P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life (P 0.003), and the MIB-1 expression with 21% per 10-unit increment (P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.

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Molecular-based classification algorithm for endometrial carcinoma to categorize ovarian endometrioid carcinoma into prognostically significant groups.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17081 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17081-e17081

Author(s):

Carlos Parra-Herran ◽

Jordan Lerner-Ellis ◽

Bin Xu ◽

Dina Bassiouny ◽

Matthew Cesari ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Mutational Analysis ◽

Survival Rates ◽

The Cancer Genome Atlas ◽

Molecular Profile ◽

Endometrioid Carcinoma ◽

Wild Type ◽

Molecular Subgroup ◽

P53 Expression ◽

Excellent Outcome

e17081 Background: The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR) and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma (OEC), their role in predicting its molecular profile and prognosis is still not fully explored. Methods: OECs resected in a 14 year period were retrieved. Only tumors with confirmed endometrioid histology and negative WT1 were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6 and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma ( B J Cancer 2015;113:299-310), cases were classified as: POLE mutated, MMR abnormal, p53 abnormal and p53 wild type. Clinicopathologic information was recorded including patient outcome. Results: 73 tumors were successfully reviewed and tested. Of these, 8 (11%) were POLE mutated, 6 (8%) were MMR abnormal and 17 (23%) were p53 abnormal; the remaining 42 cases (58%) were p53 wild type (no POLE, p53 or MMR abnormalities). Mean follow-up period was 69 months (median 62, range 1-179). The molecular classification was an independent predictor for disease free and overall survival on multivariate analysis (p = 0.005 and 0.045 respectively, Cox proportional hazard model). POLE mutated and MMR abnormal groups had 100% 5 year DFS and OS. p53 wild type cases had intermediate survival rates (86% DFS and OS). Conversely, the p53 abnormal group had worse outcomes with 42% DFS and 76% OS at 5 years. Conclusions: OEC can be classified into prognostically distinct subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 expression carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.

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Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.2002.01079.x ◽

2002 ◽

Vol 12 (1) ◽

pp. 110-118 ◽

Cited By ~ 26

Author(s):

C. Lundgren ◽

G. Auer ◽

B. Frankendal ◽

B. Moberger ◽

B. Nilsson ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Dna Content ◽

Proliferative Activity ◽

Nuclear Dna ◽

Nuclear Dna Content ◽

P53 Expression ◽

Histopathologic Features

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Endometrioid Endometrial Carcinoma With Spindle Cells–Aberrant p16 and p53 Expression

International Journal of Surgical Pathology ◽

10.1177/1066896918781730 ◽

2018 ◽

Vol 27 (2) ◽

pp. 203-207

Author(s):

Snehal Sonawane ◽

Osama Elfituri ◽

Yanmin Zhang ◽

Edgardo Yordan ◽

Nicholas Ree

Keyword(s):

Endometrial Carcinoma ◽

Spindle Cell ◽

Tumor Type ◽

Immunohistochemical Expression ◽

Cell Component ◽

Diagnostic Dilemma ◽

P53 Overexpression ◽

P53 Expression ◽

Spindle Cells ◽

Endometrioid Endometrial Carcinoma

Endometrioid carcinoma is known for its diverse morphology and may pose a diagnostic dilemma when it presents with a spindle cell component. We present a case of a 65-year-old woman with postmenopausal bleeding. Physical examination showed a mass protruding from the external cervical os. The patient underwent biopsy followed by hysterectomy. Pathologic examination showed an endometrioid endometrial carcinoma with spindle cell differentiation arising in an endometrial polyp, which raised a variety of differential diagnoses. Prior reports of this tumor type showed nonaberrant immunohistochemical expression of p16 and p53. However, this case showed p16 and p53 overexpression indicating that there is a spectrum of these tumors.

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Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200403000-00024 ◽

2004 ◽

Vol 14 (2) ◽

pp. 354-359 ◽

Cited By ~ 3

Author(s):

A. Abargel ◽

I. Avinoach ◽

V. Kravtsov ◽

M. Boaz ◽

M. Glezerman ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Immunohistochemical Staining ◽

Endometrioid Carcinoma ◽

Uterine Carcinosarcoma ◽

Clinical Value ◽

P53 Overexpression ◽

P53 Expression ◽

Epithelial Component ◽

Endometrial Carcinomas ◽

Epithelial Element

The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma.Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma.The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively).Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter.Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy.

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Endometrial Carcinoma Associated with Hyperplasia— Immunohistochemical Study of Angiogenesis and p53 Expression

Gynecologic Oncology ◽

10.1006/gyno.1998.5230 ◽

1999 ◽

Vol 72 (1) ◽

pp. 51-55 ◽

Cited By ~ 17

Author(s):

Tsunehisa Kaku ◽

Toshiharu Kamura ◽

Toshio Hirakawa ◽

Kunihiro Sakai ◽

Satoshi Amada ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Immunohistochemical Study ◽

P53 Expression

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Study of prognostic and diagnostic significance of P53 and PTEN mutation in proliferative lesions of endometrium.

Journal of Current Medical Research and Opinion ◽

10.15520/jcmro.v3i08.321 ◽

2020 ◽

Vol 3 (08) ◽

Author(s):

Dr. Suchandra Ray ◽

Dr. Ashish Jha ◽

Dr. Ayesha Afreen Islam ◽

Dr. Moumita Sengupta

Keyword(s):

Endometrial Carcinoma ◽

Endometrial Hyperplasia ◽

Premalignant Lesions ◽

Pten Gene ◽

P Value ◽

Diagnostic Significance ◽

P53 Expression ◽

Chromosome 17P13 ◽

Endometrioid Endometrial Carcinoma ◽

Endometrial Carcinomas

Background: Endometrial hyperplasia essentially implies an overgrowth of the endometrium. Complex hyperplasia associated with cellular atypia, seems to be the most important predictor of malignant potential. Endometrioid Endometrial Carcinomas account for three-fourths of Endometrial Carcinomas and are thought to develop following a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia, to hyperplasia with atypia, and finally to well-differentiated carcinoma. Currently the most frequently observed gene mutation in endometrioid carcinoma is located on chromosome 10 and is related with the PTEN gene (phoshatase and tensin homolog). PTEN inactivation is found to correlate with clonal growth pattern detected in endometrial hyperplasia and carcinoma. The p53 tumor suppressor gene locates to chromosome 17p13. The abnormal p53 expression has been found in 11% of grade 1 endometrioid endometrial carcinoma, while p53 mutations occur in 90% of non-endometrioid endometrial carcinoma. Aims and objectives: In this study we aim to evaluate the immuno histochemical expression of P53 and PTEN genes in endometrial hyperplasia and endometrial carcinoma and correlate their expression with prognostic outcomes like grade and stage, in cases of endometrial carcinoma. Material and methods: A prospective study of 60 patients with abnormal uterine bleed in the peri and post menopausal age was conducted, for a period of three years. Histological specimens were studied for HPE and IHC for the markers PTEN and P53. Results: The mean age for hyperplastic and carcinomatous lesions was 44.9 years and 53.2 years respectively. 35% (21 cases) were endometrial hyperplasia and 65% (39 cases) of cases were endometrial carcinoma. Among endometrial carcinoma 87% are of endometrioid type and 13% are of other types, which include serous, clear and malignant mixed Mullerian type of carcinoma. IHC study showed that PTEN expression is higher in endometrial hyperplasia than endometrial carcinoma cases. Elevated P53 expression correlated with poor differentiation of endometrial cancer. P53 was found to be more in cases with FIGO staging III &IV compared to stage I & II (100% vs 18.1% p value= 0.0016) and grade 3 compared to grade 1&2 (50% vs 0 p value= 0.0116). Conclusion: Immuno histochemical biomarkers like PTEN and P53 may contribute to better tumor characterization and thus more precisely determine its clinical behavior. Key words: endometrial hyperplasia, endometrial carcinoma, PTEN, P53.

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