Occult Tumor Cells in Lymph Nodes of Patients with Gastric Cancer: A Systematic Review on Their Prevalence and Predictive Role

Abstract

Background and Aims: The presence of lymph node (LN) metastasis is a key prognostic factor for gastric adenocarcinoma. However, even among patients without LN metastasis (N0), recurrence may occur. In some of these cases, occult tumor cells (OTC) are thought to play an important role. We aimed to determine the prevalence of OTC and its clinical relevance. Methods: We conducted a systematic review of studies in English published until September 2013 that addressed OTC prevalence and/or its clinical relevance. The studies were retrieved from the MEDLINE database. Results: We included 42 studies. The most frequently used methods for detecting OTC were immunohistochemical examination (IHC) and/or polymerase chain reaction (PCR) with a wide range of markers. Using IHC for OTC detection, in patients and in LN, the prevalence varied from 9 to 88% and 0.4 to 42%, respectively. With PCR, it ranged from 17 to 46% in patients, and from 3 to 33% in LN. In the studies assessing the predictive role of OTC in gastric cancer recurrence (n = 24), 8 studies found no statistical association, while 18 concluded that OTC presence was associated with poorer prognosis. However, only 6 studies presented a significantly different 5-year survival rate between patients with and without LN micrometastasis. Conclusions: OTC seems to occur in gastric cancer patients with a variable prevalence, depending on the definition, methods and setting. The majority of the retrieved studies (75%) evaluating the predictive role of OTC conclude that its presence is associated with a worse prognosis.

N staging: the role of the pathologist

“…The higher probability of micrometastasis and ITC occurrence in diffuse gastric cancer (50,55,56) potentially supports the importance of lymph node immunostaining in this cancer type. Although lymph nodes harboring IHC-detected micrometastasis are considered positive nodes in gastric carcinoma, their clinical impact is unclear (58). Gastric cancer patients classified as N0 by routine histology turned out to bear micrometastases and/or ITC after IHC have been proposed for additional treatment after surgery (59).…”

“…Gastric cancer patients classified as N0 by routine histology turned out to bear micrometastases and/or ITC after IHC have been proposed for additional treatment after surgery (59). Despite judging controversial the prognostic role of ITC in gastric cancer lymph nodes based on a review of literature, Tavares et al proposed this descriptor as a valid prognosticator provided proper definitions, methodology, stage groups, extension of lymphadenectomy and follow-up are used, implying a possible impact on therapy (58). SLN SLN navigation surgery, i.e., the removal of the first(s) lymph node(s) only along the lymphatic drainage from a malignancy, followed by a thorough pathological analysis, is an accepted standard treatment procedure for malignant melanoma and breast cancer.…”

A Prognostic Nomogram for T3N0 Rectal Cancer After Total Mesorectal Excision to Help Select Patients for Adjuvant Therapy

“…Our study also found that the prognosis of patients with >12 lymph nodes retrieved was relatively better (HR: 0.64, 95% CI: 0.56–0.72, P <0.001). New lymph node staging indicators such as metastatic lymph nodes ratio, log odds of positive lymph nodes, negative lymph node count, and lymph node micrometastasis may predict prognosis more accurately ( 52 – 56 ).…”

Molecular diagnosis of lymph node metastasis in patients with upper urinary tract cancer who underwent lymphadenectomy

“…One systematic review regarding gastric cancer concluded that eight studies found no association, whereas 18 studies found micrometastasis was associated with a poorer prognosis. However, just six studies presented a significantly different 5‐year survival rate between patients with and without micrometastasis …”