Tumorzelldissemination in das Knochenmark und in die Peritonealhohle eine immunzytochemische Untersuchung an Patienten mit einem Magen- oder kolorektalen Karzinom

Abstract

The tumor spread and the radicality of surgical resection are the most important facts in a patient's prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 x 10(5) cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Lauren type than in patients with moderately differentiated tumors (G2) or intestinal Lauren type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.

Morphological and immunohistochemical characterization of isolated tumor cells by p53 status in gastrointestinal tumors

“…Although the true incidence of early lymphatic metastasis in different tumor entities remains finally to be resolved, it has become more and more evident that approximately one third to one half of nodal-negative gastrointestinal cancer patients will exhibit ITCs in locoregional lymph nodes. The relative amount of ITCs in the bone marrow (10%) was rather low in the present report when compared to other audits where it varies broadly between 10 [35] and 82% [36], with a mean value of roughly 20 to 30%. This issue may be related to the different antibodies administered (Ber-EP4 herein vs anticytokeratin antibodies in the literature) and different amount of cells screened.…”

Cytokeratin-positive cells in bone marrow in comparison with other prognostic factors in colon carcinoma

“…Several studies have shown that IDT BM represent a prognostic deterioration of afflicted patients. However, the results are still contradictory as regards lymph glands and there are too few data as regards peritoneal lavage and venous blood [1,2,6,7,12,25]. The goal of our prospective, 6-year on-going study is to compare the rating of IDT BM with established prognosis factors so as to develop recommendations for treatment.…”

“…Immunocytochemical analysis, which various research groups have been developing for over 10 years, has also been validated in terms of its clinical relevance [1,2,4,12,14,21]. At present, this analysis is regarded as the standard method for detecting occult, early dissemination of solid tumor cells [12,14].…”

Are ‘Micrometastases’ of the Peritoneum Equivalent to Distant Metastases?

“…When using immunocytological methods disseminated tumor cells in the peritoneal cavity could be found in 20–72% of patients in a stage-dependent manner [18, 20, 21, 22, 23], the detection of tumor cells was of prognostic relevance in a number of these studies [20, 21, 23]. Schott et al [20]for example could show that the overall 4-year survival was significantly better in patients negative for immunohistochemical detection of disseminated peritoneal tumor cells in comparison to positive patients (p < 0.005).…”

“…Studies using cytology and immunocytochemistry for the detection of disseminated cells in the peritoneal cavity of colorectal cancer patients revealed a detection rate between 27 and 74% [20, 21, 22, 33]. Leather et al [33]compared tumor cell detection in peritoneal washes with conventional cytology and immunohistochemistry before and after resection of colorectal cancer: 43% of patients showed tumor cells in their peritoneal cavities, and there was no significant difference in the frequency of tumor cell detection between pre- and post-resection peritoneal lavages.…”