scholarly journals Immunohistochemical Expression of “HE4” in Endometrial Hyperplasia versus Endometrial Endometrioid Carcinoma

2021 ◽  
Vol 9 (A) ◽  
pp. 669-675
Author(s):  
Amany Talaat Abd El-Hamed ◽  
Samira Abd-Allah Mahmoud ◽  
Ahmed A. Soliman ◽  
Dina F. El-Yasergy

Aim Endometrial cancer is the most common cancer of the female genital tract. No effective biomarkers currently exist to allow for an efficient risk classification of endometrial carcinoma. Human epididymis protein 4 (HE4) overexpression is first observed in ovarian cancer tissue and subsequent research has shown that the HE4 overexpression has also been observed in patients with endometrial carcinoma. To our knowledge, this marker was evaluated in small number of research studies in cases of endometrial carcinoma versus hyperplasia. This has inspired us to test for immunohistochemical expression of HE4 in endometrial endometrioid carcinoma and hyperplastic endometria and to correlate HE4 expression with various prognostic pathological parameters including International Federation of Gynecology and Obstetrics (FIGO) grading and staging. Methods Immunohistochemical staining for HE4 was performed on paraffin-embedded sections of forty cases of endometrial endometrioid carcinoma and thirty cases of endometrial hyperplasia: including 15 cases of non-atypical hyperplasia and 15 cases of atypical hyperplasia. A histochemical score was used to evaluate HE4 expression by the tumor cells. Results In this study, HE4 overexpression level was significantly higher in endometrial endometrioid carcinoma than endometrial hyperplasia and significantly higher than non-atypical endometrial hyperplasia (P<0.05). HE4 strong expression was detected in 20% of atypical endometrial hyperplasia, but no statistical significance was detected between atypical hyperplasia and endometrial carcinoma. HE4 overexpression showed statistically significant positive correlation with FIGO grading, FIGO staging, and depth of myometrial invasion. Conclusion: During interpretation of endometrial biopsies of atypical hyperplasia, HE4 strong expression might raise the possibility of the presence of coexisting adenocarcinoma not biopsied or even warning of a near future malignant transformation. Also, strong expression of HE4 by tissue biopsy of adenocarcinoma should be reported as this might predict higher grade and stage of the tumor, a point that should be considered by surgeons while performing hysterectomy. These results should be further confirmed by extending the study on a large scale, correlation of HE4 expression with the molecular classification of Tumor Cancer Genome Atlas and long term follow up are required to establish the prognostic significance of HE4 expression in endometrial carcinoma and atypical hyperplasia. Keywords: Endometrial carcinoma, Endometrial hyperplasia, HE4, Immunohistochemistry.

2004 ◽  
Vol 14 (2) ◽  
pp. 348-353 ◽  
Author(s):  
L.-C. Horn ◽  
U. Schnurrbusch ◽  
K. Bilek ◽  
B. Hentschel ◽  
J. Einenkel

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease.The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m2), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001).Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259330
Author(s):  
Nien-Tzu Liu ◽  
Cherng-Lih Perng ◽  
Yu-Ching Chou ◽  
Pi-Shao Ko ◽  
Yi-Jia Lin ◽  
...  

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.


2020 ◽  
Vol 159 ◽  
pp. 217
Author(s):  
N. Lee ◽  
K.B. Lee ◽  
K. Kim ◽  
J.H. Hong ◽  
G.W. Yim ◽  
...  

2007 ◽  
Vol 60 (7-8) ◽  
pp. 372-376 ◽  
Author(s):  
Biljana Djordjevic ◽  
Zorica Stanojevic ◽  
Vesna Zivkovic ◽  
Dusan Lalosevic ◽  
Jasmina Gligorijevic ◽  
...  

Introduction. The aim of this study was to analyze and compare the histopathological findings in curettage and hysterectomy specimens, to evaluate the accuracy of histopathological diagnosis in curettage specimens, and to determine the frequency of coexisting endometrial carcinoma in patients with histopathological diagnosis of endometrial hyperplasia. Material and methods. Curettage and hysterectomy specimens of 135 female patients with initially diagnosed endometrial hyperplasia were retrospectively analyzed and compared. Results. Simple hyperplasia was found in 49 patients (36.3%), complex hyperplasia in 14 (10.4%), simple atypical hyperplasia in 24 (17.8%), and complex atypical hyperplasia in 48 (35.5%) patients. After hysterectomy, 59 (43.7%) patients were found to have simple hyperplasia, 12 (8.9%) complex hyperplasia, 15 (11.1%) simple atypical hyperplasia, 18 (20.7%) complex atypical hyperplasia, and 21 (15.5%) endometrial carcinoma. The accuracy of histopathological diagnosis of endometrial hyperplasia in curettage specimens was 82.2-89.6% and dependent on the types of hyperplasia. The frequency of coexisting endometrial carcinoma was significantly higher (p<0.001) in patients with atypical hyperplasia than in patients with hyperplasia without cytological atypia. After hysterectomy, coexisting endometrial carcinoma was found in 27.8% of patients with histopathological diagnosis of atypical hyperplasia in curettage specimens. In contrast to simple atypical hyperplasia, the frequency of coexisting endometrial carcinoma was significantly higher (p<0.05) in complex atypical hyperplasia. Conclusion. The frequency of coexisting endometrial carcinoma in hysterectomy specimens in patients with histopathological diagnosis of atypical hyperplasia in curettage specimens was relatively high and it should be taken into account when planning therapy. .


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