Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma.
BACKGROUND
Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases.


METHODS
We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations.


RESULTS
SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations.


CONCLUSIONS
SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.
Department of Pathology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
Miki
M
Ohe
Tomoyuki
T
Yokose
Yuji
Y
Sakuma
Yohei
Y
Miyagi
Naoyuki
N
Okamoto
Sachie
S
Osanai
Chikako
C
Hasegawa
Haruhiko
H
Nakayama
Yoichi
Y
Kameda
Kouzo
K
Yamada
Takeshi
T
Isobe
D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D046888:Tissue Array Analysis; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins