Signet Ring Cell (SRC)/Histiocytoid
carcinoma of the eyelid is a rare
neoplasm that shares histological and immunohistochemical similarities with diffuse
gastric cancer and breast
lobular carcinoma. The CDH1 gene, which encodes the
E-cadherin protein, is the best known gene associated with these
tumors. The structural and functional integrity of
E-cadherin is regulated by interconnecting molecular pathways which might participate in the development of this disease. Hence, we analyzed the
protein expression in key genes in
E-cadherin-related pathways associated with primary SRC/Histiocytoid
carcinoma of the eyelid. SRC/Histiocytoid
carcinoma diagnosed in the eyelid/orbit at MD Anderson
Cancer Center from 1990 to 2016 were evaluated. Clinicopathologic findings were studied to confirm the primary site of origin. Immunohistochemical studies for the expression of
E-cadherin, β-
catenin, c-Myc,
Cyclin D1, Src, and p53 were analyzed. Next generation sequencing for the detection of somatic mutations was performed on each
tumor with matched normal tissue, examining 50
cancer-related genes. Four primary SRC/Histiocytoid
carcinomas of the eyelid were diagnosed in four male patients aged 40-82 years. Immunohistochemically, two
tumors with loss of
E-cadherin expression had weak β-
catenin and low cytoplasmic staining for Src while the other two cases with intact
E-cadherin showed strong β-
catenin expression and high cytoplasmic expression for Src.
Cyclin D1 was focally positive in three cases. Somatic mutations in CDH1, PIK3CA, and TP53 genes were detected in two cases. Our results suggest an abnormality in the convergence of
E-cadherin/β-
catenin pathways which may promote
tumorigenesis by inducing expression of oncogenes such as
Cyclin D1 and C-Myc. Mutations in CDH1, PIK3CA, and TP53 genes could induce
E-cadherin dysfunction which takes part in the development and progression of this
malignancy.