Clinical Significance

Perhaps the greatest challenge for the development and validation of molecular assays for the detection of occult tumor cells is the demonstration of clinical utility. Carefully designed assays can successfully demonstrate the presence of tumor cells in clinical samples. Determining the clinical significance of these cells is considerably more difficult. Significant questions remain for most tumors regarding the issue of whether the presence of a small number of occult tumor cells in any sample type heralds the progression or recurrence of disease. While genomic abnormalities may indicate the presence of clearly malignant cells, protein or mRNA expression indicates cells of a particular organ or cell type, which may or may not be malignant. If malignant, these assays presently do not reflect the capacity for metastasis or progression. Additionally, the wide variation in assay protocols makes comparison of results between studies difficult.

Hundreds of studies using IHC and molecular methods to detect tumor cells have been performed. The sections below address some of the specific issues for more commonly examined sample types, and Table 28-1 summarizes a few studies, particularly those showing correlation to clinical parameters, organized by tumor type.

Table 28-1. Selected Molecular and Immunohistochemical Studies on Detection of Occult Tumor Cells

Sample Type

Finding

Reference

Breast

Blood

In patients with metastases progression-free and overall survival correlated with circulating tumor cells

28

Nodes

All histologically positive nodes and 36% of negative nodes yielded positive CK 19 RT-PCR

29

Marrow

IHC detection of CK © cells correlated with progression

30,31

Prostate

Blood

PSA RT-PCR correlation with © margins

32

RT-PCR not useful in staging, not prognostically relevant in clinically localized prostate cancer

33,34

PSA RT-PCR correlation relapse in African American men

35

RT-PCR positives reduced in response to androgen deprivation

36

Nodes

IHC and RT-PCR correlated with relapse

37,38

Marrow

RT-PCR results correlated with disease-free survival

39

Colorectal

Blood

RT-PCR results correlated with stage

40

CK 20 RT-PCR results correlated with prognosis

4

Nodes

CEA RT-PCR in stage 2 patients correlated with decreased survival

41,42

CK RT-PCR positives correlated with survival

Marrow

CK 20 RT PCR correlated with outcome

4, 40

Melanoma

Blood

RT-PCR predicted disease-free and overall survival

1

RT-PCR used to monitor interferon treatment

43

Nodes

RT-PCR upstaged 25% of patients;associated with recurrence

44

Marrow

RT-PCR an independent predictor of disease-free survival

1

Pancreas

Blood

CEA RT-PCR correlated with survival

45

Lung

Blood

RT-PCR correlated with survival, positives reduced in patients on chemotherapy

46

CK, cytokeratin;PSA, prostate-specific antigen;CEA, chorioembryonic antigen.

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