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Updated: Aug 10, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination
Alastair N J Graham1, P Maxwell, K Mulholland
1Northern Ireland Regional Department of Thoracic Surgery, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, Northern Ireland. alastair.graham@royalhospitals.n-i.nhs.uk
Aims:
In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC).
Methods:
Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34.
Results:
Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups.
Conclusion:
nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.
Insights
The nm23 gene suppresses systemic metastasis in non-small cell lung cancer (NSCLC). However, it does not appear to influence lymphatic or pleural metastasis in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- In vitro studies suggest the nm23 gene inhibits metastasis.
- Clinical evidence regarding nm23's role in metastasis is conflicting.
- Non-small cell lung cancer (NSCLC) is a major cause of cancer-related mortality.
Purpose of the Study:
- To investigate the selective influence of nm23 on systemic, pleural, and lymphatic metastasis in NSCLC.
- To clarify the contradictory findings on nm23's role in cancer metastasis.
Main Methods:
- Prospective study of 42 NSCLC patients undergoing tumor resection and lymph node sampling.
- Immunohistochemistry used to assess nm23-H1 immunoreactivity in primary tumors and detect tumor cell dissemination in bone marrow, pleural lavage, and lymph nodes.
- Microvessel count (MVC) determined using CD34 immunohistochemistry.
Main Results:
- Tumor cell dissemination detected in bone marrow (18 patients), pleura (7 patients), and lymph nodes (21 patients).
- Increased nm23 immunoreactivity in primary tumors correlated with absence of bone marrow metastasis (p=0.043).
- No significant difference in pleural or lymphatic metastasis based on nm23 levels.
Conclusions:
- nm23 acts as a suppressor of systemic metastasis in primary NSCLC.
- nm23 does not appear to suppress lymphatic or pleural metastasis in NSCLC.
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