Journal of Clinical Oncology, Vol 16, 1397-1406, Copyright © 1998 by American Society of Clinical Oncology
Novel staging protocol for non-small-cell lung cancers according to MRP- 1/CD9 and KAI1/CD82 gene expression
M Adachi, T Taki, T Konishi, CI Huang, M Higashiyama and M Miyake
Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
PURPOSE: The transmembrane-4 superfamily (TM4SF) is a recently discovered
family of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63
have been reported to modulate tumor progression or metastasis. In this
study, we investigated the relationships between these three genes, MRP-1,
KAI1, and ME491, in patients with non-small- cell lung cancers (NSCLCs).
Moreover, we assessed the prognostic value of evaluating the expressions of
MRP-1, KAI1, and ME491 simultaneously in NSCLCs. PATIENTS AND METHODS: One
hundred seventy-two patients up to stage IIIB NSCLC underwent radical
surgery during the period of January 1991 through June 1994. Using a
quantitative reverse-transcriptase polymerase chain reaction (RT-PCR)
analysis, we studied the expression of MRP-1, KAI1, and ME491 genes in
these patients. RESULTS: We found that 109 patients (63.4%) had
MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors.
Conversely, all 172 patients expressed ME491. No relationship was found
between MRP-1 expression and KAI1 expression. We classified these patients
into three groups. The 36 patients who were positive for both MRP-1 and
KAI1 were defined as group A; the 79 patients with reduced expression of
either MRP-1 or KAI1 were defined as group B, and the remaining 57 patients
with reduced expression of both MRP-1 and KAI1 were defined as group C.
This new classification was correlated with nodal status, tumor status, and
pathologic stage (P = .0056, P = .0003, and P < .0001, respectively). In
NSCLC patients, the 5-year survival rate of group A patients was
significantly better than that of group B patients and much better than
that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P <
.0001). Cox multivariate regression analysis showed that this new
classification in NSCLCs was a significant prognostic factor, as was the
nodal status (P < .0001). CONCLUSION: Our results suggest that a low
MRP-1 and KAI1 expression by tumors of the lung may be associated with poor
prognosis. It is conceivable that the evaluation for MRP-1 and KAI1
expression may identify node-negative lung cancer patients who are at high
risk for early disease recurrence, and thus need intensive adjuvant
therapy.
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