The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients

Abstract

The independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate. This study evaluated the possible association of bone marrow micrometastases with tumour progression and prognosis in patients affected by gastric cancer. Bone marrow aspirates from both iliac crests were obtained from 114 consecutive patients operated on for gastric cancer. The specimens were stained with monoclonal antibody CAM 5.2 which reacts predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33 cases (29%) had cytokeratine-positive cells in the bone marrow. There was no significant relationship between the presence of bone marrow micrometastases and site, depth of tumour invasion, lymph node metastases, presence of metastases. Patients with cytokeratine-positive cells had a trend towards a diffuse type histology (P=0.06). Among the 88 curatively resected patients, median survivals were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64 (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the presence of cytokeratine-positive cells in the bone marrow of curatively resected gastric cancer patients did not affect outcome and its independent prognostic significance remains to be proven before its official acceptance in the TNM classification.

Clinical significance of cytokeratin positive cells in bone marrow of gastric cancer patients

“…To our knowledge, this was the largest clinical study to examine BM micrometastasis of gastric cancer. CK2 has been commonly used for detecting micrometastasis in human gastrointestinal cancer, although recent data have shown that CK protein expression is down (Koch et al 2005;Weitz et al 1999;Slade et al 1999;Champelovier et al 1999;Matsunami et al 2003;Kakeji et al 1999;Macadam et al 2003;de Manzoni et al 2002). Although only 24 samples were examined, it became clear that both immunostaining and PCR showed very similar results.…”

“…Some studies showed that patients with micrometastasis had a signiWcantly worse survival rate than those without micrometastasis and a signiWcant correlation between the depth of invasion and micrometastasis (Maehara et al 1996a;Ishigami et al 2003;Yasuda et al 2002;Choi et al 2002). However, there are not many reports of micrometastasis of gastric cancer to the BM (Oki et al 2002;Maehara et al 1996b;Matsunami et al 2003;Kakeji et al 1999;Macadam et al 2003;de Manzoni et al 2002). We previously reported that cytokeratin-positive cells were detectable in the bone marrow of gastric cancers and that the microvessel density in the primary tumor doubly exceeded that of the cytokeratin-positive tumors, in comparison to Wndings in the negative tumors.…”

Recent advances in the detection of bone marrow micrometastases: A promising area for research or just another false hope? A review of the literature

“…The independent prognostic value of BM MMs has not been confirmed in all studies [68,79,82] and most of the published data are difficult to compare and interpret. Significant methodological differences, including the use of different detection methods, variable antibodies and staining procedures, study design and setting of the cutoff points seem to confound the evaluation of the otherwise impressive body of evidence favoring the prognostic value of MMs.…”

“…The prognostic value of MMs has been investigated in several previous studies comprising patients with epithelial cancers such as breast [67][68][69][70][71][72][73][74][75][76], colorectal [45,[77][78][79], gastric [80][81][82], esophageal [83][84][85][86], lung [87][88][89], ovarian [90,91], cervical [92][93][94], prostate [95], pancreatic or ampullary [96,97], as well as other forms of carcinoma, with variable results (Table 1). Among these tumors breast cancer is the most extensively studied, mostly because it is more frequently associated with late recurrences.…”

The effects of preoperative chemotherapy on isolated tumour cells in the blood and bone marrow of gastric cancer patients

“…The prognostic implications of ITC in patients with tumours of the gastrointestinal tract are controversial. In gastric cancer, ITC in the bone marrow were either significantly associated with overall survival (Jauch et al, 1996), disease-free survival (Gretschel et al, 2006), or were devoid of any prognostic value (de Manzoni et al, 2002). However, the presence of ITC is interesting not only from the prognostic point of view, but also for their potential predictive value.…”