Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma

J Formos Med Assoc. 2021 Oct;120(10):1869-1875. doi: 10.1016/j.jfma.2021.03.028. Epub 2021 Apr 18.

Abstract

Background/purpose: Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence.

Methods: Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes).

Results: Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size.

Conclusion: Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Keywords: Immunohistochemistry; Isolated tumor cells; Micrometastasis; Ovarian clear cell carcinoma; Recurrence.

MeSH terms

  • Adenocarcinoma, Clear Cell* / diagnosis
  • Adenocarcinoma, Clear Cell* / pathology
  • Female
  • Humans
  • Keratins
  • Lymph Nodes
  • Lymphatic Metastasis
  • Neoplasm Micrometastasis*
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / pathology
  • Prognosis

Substances

  • Keratins