Expression of MEL‐CAM and HSD3B1 in cervical carcinoma

To the Editor, Cancer of the uterine cervix is a common gynecologic malignancy worldwide, with two major histological types: squamous cell carcinoma (SCC) and adenocarcinoma. Cervical cancers may histologically show overlap with some gestational trophoblastic neoplasms (GTNs), particularly epithelioid trophoblastic tumors (ETTs), and placental‐site trophoblastic tumors (PSTTs), composed of neoplastic chorionic‐type intermediate trophoblastic cells and implantation site trophoblastic cells, respectively. Both GTNs and cervical cancers present in a relatively young age group (15–48 years) and almost 50% of ETTs present as a cervical or lower uterine segment mass. While hydatidiform moles have a generally good outcome, choriocarcinomas, ETT and PSTT have poorer prognoses. Treatments for these tumors require specific chemotherapy regimens, therefore distinguishing PSTTs/ ETTs from cervical cancers is vital. Several trophoblastic markers have been suggested to aid in distinguishing GTN from cervical cancers. These include β‐hCG, hPL, HLA‐G, placental alkaline phosphatase, p63, pregnancy‐specific β1‐glycoprotein (SP1), cytokeratin 18, and inhibin‐α. Two markers believed to be specific for trophoblastic cells are melanoma cell adhesion molecule (Mel‐CAM) and hydroxy‐δ‐5‐steroid dehydrogenase (HSD3B1). Mel‐CAM is a cell surface glycoprotein localized at the endothelial junction. The gene expression of Mel‐CAM is upregulated in implantation‐site trophoblastic cells making it predominantly a marker of PSTTs. HSD3B1 is a diagnostic pan‐trophoblastic marker. It is expressed in normal and neoplastic trophoblastic tissue, and hence its expression in both PSTTs and ETTs. Mao et al. show that in 95 GTN and trophoblastic lesions (such as placental site nodules and exaggerated placental site reactions), all cases were positive for HSD3B1, giving a sensitivity of 100%. Mel‐CAM is a marker for intermediate‐type trophoblasts, is therefore more useful for PSTT than ETT. In a study by Kalhor et al., of 15 intermediate trophoblast tumors and 11 choriocarcinomas, Mel‐CAM was positive in 73% and 70% of the cases, respectively. In this study, we investigated the expression of Mel‐CAM and HSD3B1 in cervical carcinoma to assess their value in distinguishing between cervical and trophoblastic tumors. Ethical approval for the use of human tissue was obtained from the Institutional Review Board of the Imperial College Healthcare NHS Trust Tissue Bank. Forty‐three cases of cervical carcinoma presenting between 2012 and 2016 were retrieved from the surgical pathology files of Hammersmith Hospital, London, UK. The median age of the patients was 41 years (range 23–83 years). Of the 42 cases of cervical tumor, there were 25 cases of SCC (58% of cases), 13 cases of adenocarcinoma (30%), and five cases of adenosquamous carcinomas (12%). Of the SCCs, 11 cases were Grade 2 (44% of SCC) and 14 cases were Grade 3 (56%). Of the adenocarcinomas, there was one case of Grade 1 (8%), 10 cases Grade 2 (77%), and two cases Grade 3 (15%). In one adenocarcinoma, the grade was not recorded. All the adenosquamous carcinomas were Grade 3. Thirty cases were staged on the histological findings. Two cases were FIGO Stage IA1, one was Stage IA2, 22 were Stage IB1, three were Stage IB2, and two were Stage 2. Tissue sections were evaluated for Mel‐CAM and HSD3B1 by immunohistochemistry. Five micro sections from formalin‐fixed, paraffin‐embedded blocks were immunostained using an automated Leica Bond 3 machine according to manufacturer's protocol. The slides incubated with 100 μl of primary antibody (anti‐Mel‐CAM antibody) 1:1000 (rabbit monoclonal, ab75769; Abcam) and anti‐HSD3B1 antibody 1:4000 (mouse monoclonal, ab55268; Abcam) at 4°C overnight. Sections of placenta and spleen/tonsil were included as positive controls for HSD3B1 and Mel‐CAM, respectively. For negative control, a duplicate slide of each tumor sample was used with 100 μl of antibody diluent and normal rabbit serum (1:8000) for HSD3B1 and Mel‐CAM, respectively. We found that Mel‐CAM was expressed in 60% of the cases, including 19 cases of the SCCs (76%), three cases of the adenocarcinomas (23%), and four cases of the adenosquamous carcinomas (80%). See Figure 1a,b for examples. Most cases showed membranous expression