Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma.
BACKGROUND
Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear.


METHODS
We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions.


RESULTS
Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007).


CONCLUSIONS
Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients.
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Shinya
S
Neri
Genichiro
G
Ishii
Tetsuhiko
T
Taira
Tomoyuki
T
Hishida
Junji
J
Yoshida
Mitsuyo
M
Nishimura
Kanji
K
Nagai
Atsushi
A
Ochiai
D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000401:mortality / Q000556:secondary / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin