GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, HNF4α expression, and KRAS mutations

Abstract

Aims

GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyze GATA6 expression in lung adenocarcinomas (LA) by immunohistochemistry (IHC) to define its association with clinicopathological characteristics.

Methods and results

IHC analysis of GATA6 was performed using tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumors other than lung cancer was also evaluated. GATA6-positivity occurred in 47 LAs (13.5%). This was observed more frequently in younger patients (p = 0.005), was associated with the absence of lymph node metastasis (p = 0.024), well to moderately-differentiated tumors (p < 0.001), the absence of lymphatic invasion (p = 0.020), and the absence of vascular invasion (p = 0.011). GATA6 expression was associated with mucin production (p < 0.001), the invasive mucinous adenocarcinoma subtype (p < 0.001), KRAS mutations (p = 0.026), positive expression of MUC2 (p < 0.001), CDX2 (p = 0.049), MUC5AC (p < 0.001), and negative expression of TTF-1 (p = 0.002). GATA6 expression was also associated with HNF4α expression (p < 0.001). Positive expression of GATA6 tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (p = 0.033). Of 270 tumors other than lung cancer, 110 expressed GATA6.

Conclusions

These findings suggested that GATA6 might interact with HNF4α and contribute to the development of mucinous type LAs.

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