In this thesis, we assess whether gastric and colorectal cancer (CRC) patients with minimal metastatic disease at the time of surgery who are at risk for disease recurrence, can be identified by... Show moreIn this thesis, we assess whether gastric and colorectal cancer (CRC) patients with minimal metastatic disease at the time of surgery who are at risk for disease recurrence, can be identified by detection of occult tumor cells (OTC) in lymph nodes or bone marrow or by analyzing the primary tumor for angiogenic and lymphangiogenic markers. Results show that the mere presence of OTC-positive lymph nodes in gastric cancer patients did not predict disease recurrence but the number of examined lymph nodes and the percentage of OTC-positive lymph nodes were independent risk factors for locoregional disease recurrence and distant disease recurrence, respectively. Automated microscopy was essential in identifying patients with OTC-positive lymph nodes. Automated microscopy was also found to be a promising tool for the detection of OTC in lymph nodes, potentially more sensitive but less specific for detecting recurrence of disease in CRC than conventional histopathology or RT-PCR. Lymph node analysis of two levels and immunohistochemical staining add to the detection of macrometastases and micrometastases in CRC. Micrometastases were found to be an independent predictor of disease recurrence but isolated tumor cells were of no prognostic significance. Disseminated tumor cells in bone marrow of patients with colorectal liver metastases detected by CK20 RT-PCR is associated with a worse clinical outcome. Sialyl Lewis X expression (sLeX) and high lymphatic microvessel density (LMVD) of the primary tumor were independent factors predicting disease recurrence in CRC. Expression of sLeX correlated with liver metastases and a high LMVD was related to regional intra-abdominal or intrapelvic lymph node metastases and distant metastases. High blood microvessel density correlated with lung metastases. These results are consistent with the notion that both lymphatic and hematogenous metastasis play a role in colorectal cancer. We conclude that patients treated for gastric or colorectal cancer who are at risk for disease recurrence can be identified through OTC detection in lymph nodes, disseminated tumor cell detection in bone marrow and analysis of angiogenic and lymphangiogenic features of the primary tumor. These findings can be implemented in new strategies for identification of high risk patients, leading to individualized therapy preventing over- and undertreatment. Show less
