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Open Access Research

Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

Miki Ohe125, Tomoyuki Yokose1*, Yuji Sakuma3, Yohei Miyagi3, Naoyuki Okamoto4, Sachie Osanai1, Chikako Hasegawa1, Haruhiko Nakayama2, Yoichi Kameda1, Kouzo Yamada2 and Takeshi Isobe5

Author Affiliations

1 Department of Pathology, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan

2 Department of Thoracic Oncology, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan

3 Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan

4 Cancer Prevention and Cancer Control Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan

5 Division of Clinical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan

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Diagnostic Pathology 2012, 7:3  doi:10.1186/1746-1596-7-3

Published: 6 January 2012

Abstract

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.

Patients and 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.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9433341526290040 webcite.

Keywords:
lung adenocarcinoma; micropapillary component; stromal micropapillary component; aerogenous micropapillary component; prognostic factor