Identification of occult tumor cells in node negative lymph nodes of colorectal cancer patients by cytokeratin 20 gene and protein expression

Abstract

CK20-specific IHC and QRT-PCR are supportive tools to conventional histology for detection of occult tumor cells in archival tissues, with the restriction that a laborious QRT-PCR procedure is necessary to achieve appropriate specificity. A prognostic value of CK20 IHC or QRT-PCR for stratification of UICC stage I and II patients into those likely to develop recurrent disease was not evident.

CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients

“…In addition, there have been several reports on the detection of CK mRNA by RT -PCR. Some studies showed a correlation between CK 20 expression detected by RT -PCR and disease recurrence as well as overall survival, whereas other studies did not (Ichikawa et al, 1998;Liefers et al, 1998;Sanchez-Cespedes et al, 1999;Bernini et al, 2000;Miyake et al, 2001;Noura et al, 2002a, b;Merrie et al, 2003;Ho et al, 2004;Lassmann et al, 2004;Pellise et al, 2004;Lee et al, 2006). As CK expression is also found in granulocytes and normal blood cells, the highly sensitive RT -PCR may produce false-positive results as described by Bostick et al (1998), Jung et al (1999) and Bustin et al (2000).…”

Detection of disseminated tumor cells in the lymph nodes of colorectal cancer patients using a real-time polymerase chain reaction assay

“…A further reason is that test sensitivity and specificity have not yet been exhaustively evaluated. The detection of a positive sample does not necessarily prove the presence of an active tumor cell but can also be the result of contamination or the presence of less active CK20-expressing cells of noncolorectal origin [25,28].…”

“…The advent of molecular approaches to tumor diagnosis has offered a myriad of new options. Attempts have been made to detect disseminated tumor cells in the blood [21,22], the lymph nodes [11, 12, 14,25], and the bone marrow [30] of patients with colorectal carcinoma using qualitative PCR assays. The results of these studies have been controversially discussed and have been found to be of limited clinical relevance only.…”

“…Although IHC is the main supplementary tool in histopathological evaluation, it often provokes discussions as to its reproducibility and its inability to provide quantitative data. In contrast, real-time PCR offers a reliable, sensitive, and faster method for quantifying the gene expression of markers in tissue samples [14,25,32].…”

“…For this reason, a multitude of studies have addressed the use of CK20 for the detection of disseminated tumor cells in the blood [21][22][23], lymph nodes [11,12,14], and bone marrow [24] of patients with colorectal carcinoma. The prognostic role of CK20-positive lymph node micrometastases has, however, been investigated in only a few studies [14,25,26]. By contrast, the specificity and sensitivity of the detection methods used in these studies has become a subject of controversial discussion when CK20 expression was found in tissues of noncolorectal origin [27][28][29].…”