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).
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432_2019_2937_MOESM1_ESM.tif
Supplementary Fig. 1 Number of cases according to %ASF. The number of the cases with %ASF 1-10% was 99. 11-20% was 19, 21-30% was10, 31-40% was 13, 41-50% was 8, 51-60% was 1, 61-70% was 3, and over 71% was 2. (TIFF 76986 kb)
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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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DOI: https://doi.org/10.1007/s00432-019-02937-9