Micrometastasis and expression of nm23 messenger RNA of lymph nodes from lung cancer and the postoperative clinical outcome.
BACKGROUND
Based on the metastatic route in lymph nodes from lung cancer, we investigated micrometastasis in the dissected lymph nodes by genetic analysis of keratin 19 and nm23-H1 (the expression of a tumor-metastatic suppressor gene) and evaluated the postoperative outcomes.


METHODS
Ten patients operated with lung cancer were 4 males and 6 females, who were stage IA; 2, stage IB; 3, stage IIA; 2, stage IIB; 1, and stage IIIA; 2, respectively. After total RNA extraction from the dissected lymph nodes, the expression of nm23-H1 and keratin 19 messenger ribonucleic acid (mRNA) were analyzed with reverse-transcripted polymerase chain reaction (RT-PCR).


RESULTS
The confirmation of micrometastasis in lymph nodes was realized in seven of 10 cases (70%), in their 5-year follow-up term. In three patients there was recurrence (43%, 3/7), and the one of them had died from the mediastinal recurrence. On the expression of nm23-H1 mRNA in lymph nodes, there was no significant difference between the pathologically lymph-node metastasis positive group and the negative one, and between the group with a tumor size over 30 mm and the group with a tumor size under 30 mm, respectively. The expression ratio of nm23-H1 gene was significantly expressed in the group with micrometastasis in lymph nodes (47%, 9/19) as compared to those without micrometastasis (10%, 1/10) (p<0.05). On the all-positive expression of nm23-H1 in the examined lymph nodes (n=4), no patient had recurrence (0%, 0/4). However, in the rest of the six patients without the all-positive expression of nm23-H1 in those lymph nodes (n=6), four patients had recurrence (67%, 4/6). There was no significance between the recurrent ratio in the all-positive expression of nm23-H1 suggesting lower incidence as compared to that in patients without all-positive expression of nm23-H1.


CONCLUSIONS
A detection of micrometastasis in lymph nodes could be a useful tool to identify the subpopulation of patients who might have a higher risk of recurrence and distant metastases. The nm23-H1 gene might be involved in a suppression role for micrometastasis in lymph nodes through the lymphatic route in lung cancer.
Second Department of Surgery, Miyazaki Medical College, Miyazaki, Japan.
Takanori
T
Ayabe
Masaki
M
Tomita
Yasunori
Y
Matsuzaki
Hironori
H
Ninomiya
Masaki
M
Hara
Tetsuya
T
Shimizu
Masao
M
Edagawa
Toshio
T
Onitsuka
Minoru
M
Hamada
D000368:Aged; D016009:Chi-Square Distribution; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D007633:Keratins; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase