p33(ING1b), a newly discovered candidate tumor suppressor gene and a
nuclear protein, belongs to the inhibitor of growth gene family. Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis,
tumor anchorage-independent growth, cellular senescence, maintenance of
genomic stability and modulation of cell cycle checkpoints. Loss of nuclear p33(ING1b) has been observed in
melanoma,
seminoma,
papillary thyroid carcinoma,
oral squamous cell carcinoma, breast ductal
cancer and
acute lymphoblastic leukemia. Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of
cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain
malignancies. Since little is known about the clinicopathological significance of p33(ING1b) in
esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new
cysteine-
histidine rich
protein (PINCH) in patients with ESCC. p33(ING1b) expression was examined by immunohistochemistry in 20 normal esophageal mucosa and in 64 ESCC specimens. The results revealed that the positive expression of p33(ING1b)
protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0.0001). Furthermore, the cases with
lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without
metastasis (P=0.001). The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P<0.0001) in ESCC, and the cases positive for both
proteins had a high
lymph node metastasis rate (P=0.001). In conclusion, p33(ING1b) cellular compartmental shift from the nucleus to the cytoplasm may cause loss of normal cellular function and play a central role in the
tumorigenesis and
metastasis of ESCC.