Human Epididymis Protein 4 in Endometrial Carcinoma
Condition: Endometrial Cancer
MeSH terms: Endometrial Neoplasms
Study type: Observational

Summary: 
      Endometrial cancer represents the most common gynecologic cancer, and it is expected to
      become an even greater public health concern as the prevalence of obesity, one of the most
      common risk factors for endometrial cancer, increases worldwide.

      Almost 20% of patients with endometrial cancer are in the premenopausal state and 10% are
      asymptomatic. In such a case, it is much harder to make an early diagnosis and usually they
      are probably diagnosed at advanced stages.

      An earlier diagnosis represents an imperative goal to improve survival and prognosis of
      patients of endometrial cancer. Actually, there are no certified screening tools for
      endometrial cancer. Pelvic ultrasound as screening for endometrial cancer-reaches 80.5% of
      sensitivity, when endometrial echo is > 5 mm, but it dramatically decreases to 20% in
      asymptomatic women; moreover, specificity is low (61%).
    

Detailed description: 
      Human epididymis protein 4, a putative protease inhibition containing two Whey Acid Protein
      domains, is significantly increased in the endometrioid subtype of endometrial carcinoma.

      Tissue microarray and polymerase chain reaction studies confirmed a high level of human
      epididymis 4 expression in both endometrioid and serous types of endometrial carcinoma ,
      these results are consistent with those from other laboratories showing increased human
      epididymis protein 4 messenger ribonucleic acid and protein expression in endometrial cancer
      tissues.

      Subsequent investigation demonstrated that human epididymis protein 4 are detectable in
      various normal tissues with varying expression levels, yet their levels are significantly
      increased in endometrial carcinoma compared to normal endometrium.

      Human epididymis protein 4 ( HE4) is a member of the whey-acidic protein family and it is .
      Human epididymis protein 4 was first isolated from the human epididymis .

      This protein is also known as epididymal secretory protein E4, major epididymis specific
      protein E4 and putative protease inhibitor WAP5. WFDC-2 gene product was originally thought
      to be a protein specifically expressed in the epididymis and was dubbed as a tissue marker
      for the same.

      Angioli etal 2013, found HE4 cutoff of 70pmol/l yields the best sensitivity and specificity
      for detecting endometrial cancer (59.4%) sensitivity and 100% specificity) with a positive
      predictive value 100% and negative predictive value equal to 71.52% for the 70 pmol/l cutoff,
      also found that HE4 marker was never increased in patients with benign diseases Kalogera etal
      2012 found that HE4 is elevated in high proportion of endometrial cancer patients and it is
      correlated with myometrial invasion (> 50% P< 0.00) also found that lymph node, statue
      correlates with the HE4 values there is a statistical significant difference comparing stage
      I versus stage III (P < 0.0010).

      These findings suggest that HE4 could be useful as a preoperative indicator to identify
      patients suitable for pelvic and para aortic lymphadenectomy.
    

Intervention name(s): Human epididymis protein 4
Intervention type(s): Diagnostic Test
Intervention description(s): Human epididymis protein will be quantitatively assayed using the enzyme immunometric assay (EIA) method
Other intervention name(s): Major epididymis specific protein E4; putative protease inhibitor WAP5
Intervention MeSH terms: Protease Inhibitors
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        1- History taking, general examination , pelvic ultrasound will be done for all patients
        under the study,endometrial biopsy will be obtained form all patients and will be reviewed
        by the pathologists.

        6- Computed axial tomography (CT scan) will be done for patient with endometrial carcinoma
        (case study) for detect tumor as a part of metastatic workup.

        7- Pre-operative complete investigation will be done for patient underwent staging
        lapratomy (CBC, kidney function tests , liver function tests, FBS and coagulation profile
        to rule out systemic causes of bleeding.

        8- Blood sample will be taken from all patients to assess serum level of HE4.
      
Biospecimen description: 
      blood sample for polymerase chain reaction for human epididymis protein 4. endometrial sample
      in formalin for pathological examination
    
Keywords: Epididymal secretory protein E4; Major epididymis specific protein E4