Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer

Abstract

Objective To evaluate the utility of serum (HE4) as a marker for high risk disease in patients with endometrial cancer (EC). Methods Preoperative serum HE4 levels were measured from a cohort of 75 patients surgically treated for EC. Cases were compared to matched controls without a history of cancer. HE4 levels were analyzed as a function of primary tumor diameter, grade, stage and histological subtype. Wilcoxon rank-sum test, ROC curve, Spearman rank correlation coefficient and contingency tables were used for statistical analyses. Results Stage distribution was as follows: 49 stage I, 2 stage II, 20 stage III, 4 stage IV. Type I EC was present in 54 patients, type II in 21. Median HE4 was significantly elevated in both type I and II EC compared to controls (P<0.001 and P=0.019, respectively). There was significant correlation between type I EC, median HE4, deep myometrial invasion (MI) (>50%, P<0.001) and primary tumor diameter (PTD) (>2cm, P=0.002). Low risk patients (type I, MI ≤50% and PTD ≤2cm) had significantly lower median HE4 compared to all other type I EC patients (P<0.01). In comparison to prior investigations, HE4 (cutoff of 8 mfi) was more sensitive than CA125 in detecting advanced stage disease. Conclusion Our data suggest that HE4 is elevated in a high proportion of EC patients, is correlated with PTD and MI, and is more sensitive than CA125 in EC. These observations suggest potential utility of HE4 in the preoperative prediction of high risk disease and the necessity for definitive surgical staging.

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

“…Interestingly, HE4 -V0, the most abundant HE4 variant, was found to be correlated with age in the endometrioid cancer cohort. This result is consistent with another study showing that serum HE4 levels are closely correlated with age in EC patients [ 46 ]. Given the fact that the relationship between HE4 mRNA levels and age is not evident in the normal control group, this age-related change of HE4 levels may reflect tumor characteristics rather than varying hormonal status.…”

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

“…Interestingly, HE4 -V0, the most abundant HE4 variant, was found to be correlated with age in the endometrioid cancer cohort. This result is consistent with another study showing that serum HE4 levels are closely correlated with age in EC patients [ 46 ]. Given the fact that the relationship between HE4 mRNA levels and age is not evident in the normal control group, this age-related change of HE4 levels may reflect tumor characteristics rather than varying hormonal status.…”

Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

“…These findings suggest that HE4 could serve as a preoperative indicator showing the need for pelvic and para-aortic lymphadenectomy. These results are consistent with the study by Kalogera et al and Moore et al who showed that HE4 levels were closely associated with myometrial invasion and lymph node dissection [21,32]. In our study the best threshold value of serum HE4 to distinguish patients with stage IA from others with an early stage disease (sensitivity 86.6% and NPV of 88.4) was 78 pmol/l.…”

Human Epididymis Protein 4 Predicted Concurrent Intermediate-high-risk Endometrial Cancer and Eligibility of Fertility-sparing Treatment for Patients Diagnosed with Endometrial Atypical Hyperplasia Before Surgery

“…In final-EC patients, increased HE4 levels were related to more severe pathological features including deeper myometrial invasion, MELF positivity, larger tumor size, and intermediate-high-risk EC. These findings aligned with previous studies on EC patients 9 , 30 , suggesting that HE4 might predict poor outcomes in preoperative-EAH patients.…”

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

“…Interestingly, HE4 -V0, the most abundant HE4 variant, was found to be correlated with age in the endometrioid cancer cohort. This result is consistent with another study showing that serum HE4 levels are closely correlated with age in EC patients [ 46 ]. Given the fact that the relationship between HE4 mRNA levels and age is not evident in the normal control group, this age-related change of HE4 levels may reflect tumor characteristics rather than varying hormonal status.…”

Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

“…These findings suggest that HE4 could serve as a preoperative indicator showing the need for pelvic and para-aortic lymphadenectomy. These results are consistent with the study by Kalogera et al and Moore et al who showed that HE4 levels were closely associated with myometrial invasion and lymph node dissection [21,32]. In our study the best threshold value of serum HE4 to distinguish patients with stage IA from others with an early stage disease (sensitivity 86.6% and NPV of 88.4) was 78 pmol/l.…”

Human Epididymis Protein 4 Predicted Concurrent Intermediate-high-risk Endometrial Cancer and Eligibility of Fertility-sparing Treatment for Patients Diagnosed with Endometrial Atypical Hyperplasia Before Surgery

“…In final-EC patients, increased HE4 levels were related to more severe pathological features including deeper myometrial invasion, MELF positivity, larger tumor size, and intermediate-high-risk EC. These findings aligned with previous studies on EC patients 9 , 30 , suggesting that HE4 might predict poor outcomes in preoperative-EAH patients.…”

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

“…Interestingly, HE4 -V0, the most abundant HE4 variant, was found to be correlated with age in the endometrioid cancer cohort. This result is consistent with another study showing that serum HE4 levels are closely correlated with age in EC patients [ 46 ]. Given the fact that the relationship between HE4 mRNA levels and age is not evident in the normal control group, this age-related change of HE4 levels may reflect tumor characteristics rather than varying hormonal status.…”

Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy

“…These findings suggest that HE4 could serve as a preoperative indicator showing the need for pelvic and para-aortic lymphadenectomy. These results are consistent with the study by Kalogera et al and Moore et al who showed that HE4 levels were closely associated with myometrial invasion and lymph node dissection [21,32]. In our study the best threshold value of serum HE4 to distinguish patients with stage IA from others with an early stage disease (sensitivity 86.6% and NPV of 88.4) was 78 pmol/l.…”

Human Epididymis Protein 4 Predicted Concurrent Intermediate-high-risk Endometrial Cancer and Eligibility of Fertility-sparing Treatment for Patients Diagnosed with Endometrial Atypical Hyperplasia Before Surgery

“…In final-EC patients, increased HE4 levels were related to more severe pathological features including deeper myometrial invasion, MELF positivity, larger tumor size, and intermediate-high-risk EC. These findings aligned with previous studies on EC patients 9 , 30 , suggesting that HE4 might predict poor outcomes in preoperative-EAH patients.…”