Detection of Occult Lymph Node Tumor Cells in Node-Negative Gastric Cancer Patients

Abstract

Background: The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. Aim: To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion: The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging.

Clinicopathological and prognostic features of Epstein‐Barr virus infection, microsatellite instability, and PD‐L1 expression in gastric cancer

“…The mean number of LNs retrieved was high, attesting the high quality surgery and pathology, and the low risk of understaging. This risk was even reduced, since IHC for cytokeratin was performed for the detection of occult tumor cells in selected cases . To avoid loss and provide a representation of different tumor areas, we used a large number of cores per case.…”

“…Surgical specimens were fixed in 10% buffered formalin or Carnoýs Solution and were evaluated according to the College of American Pathologists protocol . IHC with cytokeratin were performed in some cases to detect lymph node micrometastases . Tumor stage was defined according to the 7th edition of the TNM as proposed by the International Union Against Cancer (UICC) …”

“…13 IHC with cytokeratin were performed in some cases to detect lymph node micrometastases. 14 The study was approved by the hospital ethics committee (NP771/2015) and is registered in the "Plataforma Brasil" (a National Research Council) under the CAAE number 43453515.6.0000.0065.…”

Impact of multisection and immunohistochemistry in lymph node staging of Gastric Carcinoma – Case series

“…It may vary not only by factors directly related to the tumor itself but also by the method used for their identification. It is believed that LNmicrometastases may be responsible for tumor recurrence in patients whose tumors were resected entirely, even in cases in which there were no LN metastases 13,14 .…”

“…Other studies assessing the presence of micrometastases, not only in GC but also in colonic, esophageal, head and neck, and gynecological tumors, also observed the same findings. Such studies attest that, regardless of the tumor staging, the conventional histological evaluation, which is based on just one cut in the LN structure, does not stage the metastatic LN involvement adequately 13,15,16,25 .…”