Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients

Yusuke Takahashi, Genichiro Ishii, Tetsuhiko Taira, Satoshi Fujii, Shinya Yanagi, Tomoyuki Hishida, Junji Yoshida, Mitsuyo Nishimura, Hiroaki Nomori, Kanji Nagai, Atsushi Ochiai

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome. Methods: A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma" with those of the SqCC cells surrounded by "thin stroma." Results: The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033). Conclusion: SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.

Original languageEnglish
Pages (from-to)1460-1467
Number of pages8
JournalJournal of Thoracic Oncology
Volume6
Issue number9
DOIs
Publication statusPublished - 2011 Sep
Externally publishedYes

Fingerprint

Squamous Cell Carcinoma
Lung
Neoplasms
Fibroblasts
Matrix Metalloproteinase 7
Tumor Microenvironment
Survival
Laminin
Cadherins
Stromal Cells
Multivariate Analysis
Phenotype
Recurrence

Keywords

  • Epithelial mesenchymal transition
  • Fibrous stroma
  • Prognostic indicator
  • Squamous cell carcinoma
  • Vascular invasion

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients. / Takahashi, Yusuke; Ishii, Genichiro; Taira, Tetsuhiko; Fujii, Satoshi; Yanagi, Shinya; Hishida, Tomoyuki; Yoshida, Junji; Nishimura, Mitsuyo; Nomori, Hiroaki; Nagai, Kanji; Ochiai, Atsushi.

In: Journal of Thoracic Oncology, Vol. 6, No. 9, 09.2011, p. 1460-1467.

Research output: Contribution to journalArticle

Takahashi, Y, Ishii, G, Taira, T, Fujii, S, Yanagi, S, Hishida, T, Yoshida, J, Nishimura, M, Nomori, H, Nagai, K & Ochiai, A 2011, 'Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients', Journal of Thoracic Oncology, vol. 6, no. 9, pp. 1460-1467. https://doi.org/10.1097/JTO.0b013e318229189d
Takahashi, Yusuke ; Ishii, Genichiro ; Taira, Tetsuhiko ; Fujii, Satoshi ; Yanagi, Shinya ; Hishida, Tomoyuki ; Yoshida, Junji ; Nishimura, Mitsuyo ; Nomori, Hiroaki ; Nagai, Kanji ; Ochiai, Atsushi. / Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 9. pp. 1460-1467.
@article{26926ecb3e62412f999cf1d8d7586115,
title = "Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients",
abstract = "Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome. Methods: A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, {"}fibrous stroma type{"} (n = 85), and {"}thin stroma type{"} (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by {"}fibrous stroma{"} with those of the SqCC cells surrounded by {"}thin stroma.{"} Results: The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033). Conclusion: SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.",
keywords = "Epithelial mesenchymal transition, Fibrous stroma, Prognostic indicator, Squamous cell carcinoma, Vascular invasion",
author = "Yusuke Takahashi and Genichiro Ishii and Tetsuhiko Taira and Satoshi Fujii and Shinya Yanagi and Tomoyuki Hishida and Junji Yoshida and Mitsuyo Nishimura and Hiroaki Nomori and Kanji Nagai and Atsushi Ochiai",
year = "2011",
month = "9",
doi = "10.1097/JTO.0b013e318229189d",
language = "English",
volume = "6",
pages = "1460--1467",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "9",

}

TY - JOUR

T1 - Fibrous stroma is associated with poorer prognosis in lung squamous cell carcinoma patients

AU - Takahashi, Yusuke

AU - Ishii, Genichiro

AU - Taira, Tetsuhiko

AU - Fujii, Satoshi

AU - Yanagi, Shinya

AU - Hishida, Tomoyuki

AU - Yoshida, Junji

AU - Nishimura, Mitsuyo

AU - Nomori, Hiroaki

AU - Nagai, Kanji

AU - Ochiai, Atsushi

PY - 2011/9

Y1 - 2011/9

N2 - Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome. Methods: A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma" with those of the SqCC cells surrounded by "thin stroma." Results: The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033). Conclusion: SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.

AB - Cancer tissue is composed of various stromal cells forming cancer-specific microenvironments. Peritumoral stroma is reportedly composed of activated fibroblasts that can influence the biological properties of tumor cells, mainly their local aggressiveness and their ability. The aim of this study was to examine whether the histological properties of peritumoral stroma are correlated with squamous cell carcinoma (SqCC) aggressiveness and clinical outcome. Methods: A series of 220 pathological stage I lung SqCC were categorized into two types according to the histological properties of the peritumoral stroma, "fibrous stroma type" (n = 85), and "thin stroma type" (n = 135), and compared the prognostic significance. Furthermore, we compared the immunohistochemical properties of the SqCC cells surrounded by "fibrous stroma" with those of the SqCC cells surrounded by "thin stroma." Results: The prognosis of the patients with fibrous stroma-type tumors was significantly poorer than that of the thin stroma type with regard to both recurrence-free survival (p = 0.005) and overall survival (p = 0.008). A multivariate analysis showed that the presence of a fibrous stroma was an independent prognostic factor (p = 0.030). Compared with the SqCC cells with a thin stroma, the SqCC cells with a fibrous stroma exhibited reduced expression of E-cadherin (55.9 versus 126.0, p < 0.001) and an increased expression of laminin-5γ2 (94.6 versus 25.0, p = 0.001), matrix metalloproteinase-7 (26.0 versus 3.50, p = 0.009), and c-Met (64.0 versus 36.5, p = 0.033). Conclusion: SqCC with a fibrous stroma displayed higher invasive phenotype and were associated with a significantly poor prognosis. The current results suggest that the microenvironment created by both SqCC cells and the peritumoral fibroblasts may facilitate cancer aggressiveness.

KW - Epithelial mesenchymal transition

KW - Fibrous stroma

KW - Prognostic indicator

KW - Squamous cell carcinoma

KW - Vascular invasion

UR - http://www.scopus.com/inward/record.url?scp=80052230639&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052230639&partnerID=8YFLogxK

U2 - 10.1097/JTO.0b013e318229189d

DO - 10.1097/JTO.0b013e318229189d

M3 - Article

VL - 6

SP - 1460

EP - 1467

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 9

ER -