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Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical Outcome

View Article: PubMed Central - PubMed

ABSTRACT

Background: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients.

Methods: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated.

Results: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090–5.233; p=0.030).

Conclusion: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.

No MeSH data available.


Related in: MedlinePlus

Histologic parameters and patterns of keratinization applied in this study. Tumor budding is observed along tumor edge (A); this is defined as the presence of structures comprising fewer than five tumor cells (arrowheads) at higher magnification (B). Single cell invasion (C) and large nuclei (cancer cell nucleus >4 times than that of a small lymphocyte) (D), nonkeratinization (entire tumor area, <5% keratinization) (E), cytoplasmic keratinization (F), keratin pearl (G), and layered keratinization (H) (H&E stain; A, ×40; B–D, ×400; E–H, ×200).
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Figure 1: Histologic parameters and patterns of keratinization applied in this study. Tumor budding is observed along tumor edge (A); this is defined as the presence of structures comprising fewer than five tumor cells (arrowheads) at higher magnification (B). Single cell invasion (C) and large nuclei (cancer cell nucleus >4 times than that of a small lymphocyte) (D), nonkeratinization (entire tumor area, <5% keratinization) (E), cytoplasmic keratinization (F), keratin pearl (G), and layered keratinization (H) (H&E stain; A, ×40; B–D, ×400; E–H, ×200).

Mentions: All tissue slides were subjected to hematoxylin and eosin staining and evaluated for the presence of the following recently identified poor prognostic factors: tumor budding, single cell invasion, and large nuclei5. Initially, the entire tumor set was scanned at ×100 magnification and subjected to a detailed review. First, tumor budding, or the presence of small tumor nests comprising fewer than five tumor cells, were counted in 10 high-power fields (HPFs) at ×200 magnification. We defined a high grade of tumor budding as more than eight tumor budding events per 10 HPFs (Figure 1A, B). Single cell invasion was also evaluated at ×200 magnification (Figure 1C), and nuclear features were assessed at ×400 magnification. We calculated the average nuclear diameter of at least 100 tumor cells in at least three HPFs per sample. A large nucleus was defined as a diameter greater than that of four small lymphocytes (Figure 1D).


Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical Outcome
Histologic parameters and patterns of keratinization applied in this study. Tumor budding is observed along tumor edge (A); this is defined as the presence of structures comprising fewer than five tumor cells (arrowheads) at higher magnification (B). Single cell invasion (C) and large nuclei (cancer cell nucleus >4 times than that of a small lymphocyte) (D), nonkeratinization (entire tumor area, <5% keratinization) (E), cytoplasmic keratinization (F), keratin pearl (G), and layered keratinization (H) (H&E stain; A, ×40; B–D, ×400; E–H, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392489&req=5

Figure 1: Histologic parameters and patterns of keratinization applied in this study. Tumor budding is observed along tumor edge (A); this is defined as the presence of structures comprising fewer than five tumor cells (arrowheads) at higher magnification (B). Single cell invasion (C) and large nuclei (cancer cell nucleus >4 times than that of a small lymphocyte) (D), nonkeratinization (entire tumor area, <5% keratinization) (E), cytoplasmic keratinization (F), keratin pearl (G), and layered keratinization (H) (H&E stain; A, ×40; B–D, ×400; E–H, ×200).
Mentions: All tissue slides were subjected to hematoxylin and eosin staining and evaluated for the presence of the following recently identified poor prognostic factors: tumor budding, single cell invasion, and large nuclei5. Initially, the entire tumor set was scanned at ×100 magnification and subjected to a detailed review. First, tumor budding, or the presence of small tumor nests comprising fewer than five tumor cells, were counted in 10 high-power fields (HPFs) at ×200 magnification. We defined a high grade of tumor budding as more than eight tumor budding events per 10 HPFs (Figure 1A, B). Single cell invasion was also evaluated at ×200 magnification (Figure 1C), and nuclear features were assessed at ×400 magnification. We calculated the average nuclear diameter of at least 100 tumor cells in at least three HPFs per sample. A large nucleus was defined as a diameter greater than that of four small lymphocytes (Figure 1D).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients.

Methods: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated.

Results: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090&ndash;5.233; p=0.030).

Conclusion: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.

No MeSH data available.


Related in: MedlinePlus