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Growth patterns of small peripheral squamous cell carcinoma of the lung and their impacts on pathological and biological characteristics of tumor cells

Abstract

Purpose

The growth pattern of peripheral squamous cell carcinoma (SCC) of the lung is divided into two types: alveolar space-filling (ASF) growth and alveolar space-destructive (ASD) growth. The aim of this study was to investigate the clinicopathological differences between cancer cells displaying ASF and ASD growth.

Methods

We analyzed 155 patients with peripheral SCC measuring 30 mm or less in diameter. The proportion of ASF in the total tumor area (%ASF) was determined using digital image analysis. We examined the clinicopathological characteristics of the cancer cells and compared the immunophenotypes of high %ASF tumors (> 30%) and low %ASF tumors (0%). Finally, we analyzed the prognostic impact of ASD area with small SCC cases (≤ 2.0 cm, n = 72).

Results

Cases of high %ASF tumors showed significantly lower frequencies of lymphovascular invasion (p = 0.008). Immunohistochemical staining revealed that the expression score of laminin-5, invasive-related molecule, in cancer cells was significantly lower in high %ASF cases than in low %ASF cases (p = 0.001). Within the same tumor, laminin-5 expression in the ASF area was significantly lower than that in the ASD area (p = 0.001). The overall 5-year survival rate of patients with a larger ASD area (> 1.0 cm2) was significantly lower than that of patients with a smaller ASD area (≤ 1.0 cm2) (p = 0.017).

Conclusions

In this study, we clearly showed that cancer cells presenting with ASF represents a “less invasive phenotype” in peripheral SCC.

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Abbreviations

ASF:

Alveolar space filling

ASD:

Alveolar space destructive

CD204(+) TAMs:

CD204-positive tumor-associated macrophages

CAFs:

Cancer-associated fibroblasts

CAIX:

Carbonic anhydrase IX

EMT:

Epithelial–mesenchymal transition

GLUT-1:

Glucose transporter 1

LV:

Lymphovascular

PL:

Pleural involvement

PD-L1:

Programmed death-ligand 1

PDPN:

Podoplanin

SCC:

Squamous cell carcinoma

SPSS:

Statistical Package for Social Science

VVG:

Victoria blue van Gieson

HR:

Hazard ratio

95% CI:

95% Confidence interval

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Funding

This study was supported in part by the National Cancer Center Research and Development Fund (29-A-9) and JSPS KAKENHI (16H05311).

Author information

Correspondence to Genichiro Ishii.

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The authors have no conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Omori, T., Aokage, K., Nakamura, H. et al. Growth patterns of small peripheral squamous cell carcinoma of the lung and their impacts on pathological and biological characteristics of tumor cells. J Cancer Res Clin Oncol 145, 1773–1783 (2019). https://doi.org/10.1007/s00432-019-02937-9

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Keywords

  • Peripheral lung cancer
  • Squamous cell carcinoma
  • Alveolar space filling (ASF)
  • Alveolar space destructive (ASD)