Micrometastasis in the bone marrow of patients with lung cancer associated with a reduced expression of E-cadherin and beta-catenin: risk assessment by immunohistochemistry.
BACKGROUND
The presence of disseminated tumor cells in bone marrow is considered to be a premetastatic state, which is called micrometastasis. To evaluate the relationship between micrometastasis and cellular adhesion molecules in the primary lesion, E-cadherin and beta-catenin were immunohistochemically investigated. Methods. Fifty-eight patients with non-small cell lung cancer who underwent a complete resection were entered into this study. Tumor cells in bone marrow aspirates were detected by immunohistochemistry using cytokeratin (CK) 18. Immunohistochemical studies of E-cadherin and beta-catenin were performed in the corresponding primary tumor.


RESULTS
CK-positive cells were detected in the bone marrow aspirates from 27 of 58 patients. A reduced expression of the E-cadherin and beta-catenin was found in 16 (27.6%) and in 22 (37.9%) of 58 patients, respectively. In 26 cases with a reduced expression of E-cadherin and/or beta-catenin, 16 cases had CK-positive cells, whereas 11 of 32 cases with normal expression of both factors had CK-positive cells (P=.0392). The patients with micrometastasis demonstrated an earlier recurrence (P =.0642) and a significantly poorer survival (P =.0437) than those without such cells.


CONCLUSIONS
Micrometastasis in the bone marrow might be a significant predictor of poor prognosis, and a reduced expression of E-cadherin and beta-catenin are important determinants for the metastatic capability of individual cancer cells.
Sugio
Kenji
K
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kase
Shinichiro
S
Sakada
Takashi
T
Yamazaki
Koji
K
Yamaguchi
Masafumi
M
Ondo
Kaoru
K
Yano
Tokujiro
T
D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000401:mortality / Q000556:secondary*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D007633:Keratins