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Erschienen in: Journal of Cancer Research and Clinical Oncology 1/2016

01.01.2016 | Original Article – Cancer Research

Drastic morphological and molecular differences between lymph node micrometastatic tumors and macrometastatic tumors of lung adenocarcinoma

verfasst von: Nao Aramaki, Genichiro Ishii, Eiji Yamada, Masahiro Morise, Keiju Aokage, Motohiro Kojima, Tomoyuki Hishida, Junji Yoshida, Norihiko Ikeda, Masahiro Tsuboi, Atsushi Ochiai

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2016

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Abstract

Purpose

The expansion of micrometastatic tumors to macrometastatic ones is thought to be tightly regulated by several microenvironmental factors. The aim of this study was to elucidate the morphological and phenotypical differences between micrometastatic and macrometastatic tumors.

Method

We first examined the morphological characteristics of 66 lymph node (LN) micrometastatic tumors (less than 2 mm in size) and 51 macrometastatic tumors (more than 10 mm in size) in 42 lung adenocarcinoma cases. Then, we evaluated the expression level of E-cadherin, S100A4, ALDH1, and Geminin in cancer cells and the number of smooth muscle actin (SMA), CD34, and CD204 (+) stromal cells in the primary tumors, matched micrometastatic tumors, and macrometastatic tumors (n = 34, each).

Results

Tumor budding reflects the process of EMT, and stromal reactions were observed more frequently in macrometastatic tumors (P < 0.001). E-cadherin staining score for the micrometastatic tumors was significantly higher than that for the primary tumors (P < 0.001). In contrast, the E-cadherin staining score for the macrometastatic tumors was significantly lower than that for the micrometastatic tumors (P = 0.017). As for the stromal cells, the numbers of SMA (+) fibroblasts, CD34 (+) microvessels, and CD204 (+) macrophages were significantly higher for the macrometastatic tumors and primary tumors than for the micrometastatic tumors (P < 0.001, all).

Conclusion

The present study clearly showed that dynamic microenvironmental changes (e.g., EMT-related changes in cancer cells and structural changes in stromal cells) occur during the growth of micrometastases into macrometastases.
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Metadaten
Titel
Drastic morphological and molecular differences between lymph node micrometastatic tumors and macrometastatic tumors of lung adenocarcinoma
verfasst von
Nao Aramaki
Genichiro Ishii
Eiji Yamada
Masahiro Morise
Keiju Aokage
Motohiro Kojima
Tomoyuki Hishida
Junji Yoshida
Norihiko Ikeda
Masahiro Tsuboi
Atsushi Ochiai
Publikationsdatum
01.01.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2016
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-015-1996-0

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