Micrometastases detection

Steinhoff MM. Axillary node micrometastases Detection and biologic significance. Breast J. 1999 5 325-329. 

Metastasis is a process by which malignant cells leave their primary site and spread to distant locations throughout the body. It is the formation of metastasis that makes cancer such a lethal disease. The presence of metastasis is therefore the main cause of morbidity and mortality in patients with cancer. While primary tumors are potentially resectable, most metastases are resistant to all current forms of cancer treatment. Approximately 30% of patients with newly diagnosed solid cancers (excluding nonmelanoma skin cancers) have clinically detectable metastases, while another 30% may have occult micrometastases (L2). Clearly, to reduce mortality from cancer, we have to be able to prevent or treat metastasis. 

Nomoto S, et al. Chnical application of K-ras oncogene mutations in pancreatic carcinoma detection of micrometastases. Semin Surg Oncol 1998 15(l) 40-46. 

Rapid immunohistochemical study of frozen sections is necessary for intraoperative diagnosis in some cases. Rapid immunostaining is also helpful in confirming or excluding tumor clearance in resection margins or in detecting micrometastases in sentinel lymph nodes in breast cancer patients. Two methods to immunostain frozen sections are the enhanced polymer one-step staining (EPOS) system and the EnVision system both systems are detailed later. 

Lin, W. C., Pretlow, T. P., Pretlow, T. G. 2d and Culp, L. A. (1990a) Development of micrometastases earliest events detected with bacterial lacZ gene-tagged tumor cells. J. Natl. Cancer Inst. 82,1497-1503. 

However, the high incidence of later recurrence implies that the primary tumor began to metastasize before it was removed. These early metastases are too small to detect with currently available diagnostic tests and are known as micrometastases. Adjuvant therapy is defined as the use of systemic agents to eradicate micrometastatic... 

By the time cancer becomes clinically detectable, it is advanced (about 30 doublings) and has had ample opportunity to establish distant micrometastases. 

MOLECULAR METHOD TO QUANTITATIVELY DETECT MICROMETASTASES AND ITS CLINICAL SIGNIFICANCE IN GASTROINTESTINAL MALIGNANCIES... 

Recurrence of tumors after curative surgery is a life-threatening event for cancer patients, and the prevention of such recurrence is one of the most important problems to be resolved at the clinical level. The major cause of recurrence after curative resection in cancer patients is considered to be free tumor cells in the body fluid and invisible micrometastases in the distant organs which were already present at the time of removal of the primary neoplasm or had been shed from the primary tumor during surgical manipulation. To prevent recurrence and improve survival rates of cancer patients after curative resection, careful detection and subsequent chemotherapy for micrometastasis may be promising. To date, however, conventional adjuvant... 

For detection of micrometastasis, immunohistochemical method was first introduced in 1987 (S3) and has been evaluated as a reliable method because the presence of tumor cells can be confirmed visually based on their morphology. To date, this immunohistochemical method is still widely used for detection of micrometastases in the lymph nodes and bone marrow (T3). 

In the field of colorectal cancer, there are over 15 reports on the immunohistochemical detection of micrometastasis in the lymph node (Al, Ol). Most studies concluded that immunohistochemically detected micrometastasis does not correlate with a poorer outcome. However, the prognostic significance of immunohistochemically detected micrometastases remains still controversial (G7, S2), similar to that for gastric cancer. 

A3. Aoki, S., Takagi, Y., Hayakawa, M., Yamaguchi, K., Futamura, M., Kunieda, K., etal.. Detection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients. J. Exp. Clin. Cancer Res. 21, 555-562 (2002). 

F4. Fukagawa, T., Sasako, M., Mann, G. B., Sano, T., Katai, H., Maruyama, K., et al., Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma. Cancer 92, 753-760 (2001). 

K9. Kubota, K., Nakanishi, H., Hiki, N., Shimizu, N., Tsuji, E., Yamaguchi, H., et al.. Quantitative detection of micrometastases in the lymph nodes of gastric cancer patients with real-time RT-PCR A comparative study with immunohistochemistry. Int. J. Cancer 105, 136-143 (2003). 

M9. Mori, M., Mimori, K., Inoue, H., Barnard, G. F., Tsuji, K., Nanbara, S., et al.. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res. 55, 3417-3420 (1995). 

O., et al. Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. 

Okada, Y., Fujiwara, Y., Yamamoto, H., Sugita, Y., Yasuda, T., Doki, Y., et al. Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay. Cancer 92, 2056-2064 (2001). 

Schoenfeld, A., Luqmani, Y., Smith, D., O Reilly, S., Shousha, S., Sinnett, H. D., etal.. Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction. Cancer Res. 54, 2986-2990 (1994). 

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