Several studies have reported a high SCCA expression in HCC tissues [13, 14]. Giannelli et al  measured serum SCCA in 120 HCC patients, 90 cirrhotics, and 41 healthy subjects. SCCA levels were significantly elevated in HCC patients compared to cirrhotic or normal subjects. The sensitivity and specificity for SCCA in HCC diagnosis were 84% and 46%, respectively. Guido et al  demonstrated aberrant expression of SCCA in HCC and provided evidence that SCCA overexpression is an early event in liver cell carcinomatous transformation was consistently detected in all considered dysplastic nodules.
The high SCCA expression in HCC tissue seems remarkable since the liver does not possess squamous epithelial cells, although hepatocytes share a common embryogenic origin. Furthermore, the role of serpins in neoplastic cells indicates that SCCA expression makes cancer cells resistant to several killing mechanisms by inhibition of apoptosis . The SCCA antigen represents a marker for more advanced organ tumors such as the cervix, lung and oropharynx . A significant association was also noted between SCCA overexpression and histological grade 2/3 HCC, suggesting SCCA as a marker of cancer aggressiveness .
However, in our HCC patient cohort, positive SCCA staining was associated with an improved survival rate. We found that negative SCCA staining was associated with a higher Ki67 score. In multiple logistic regression analysis, the Ki67 and the TUNEL scores were significant independent predictors of negative SCCA staining. A previous study established that Ki-67 immunostaining of HCC lesions was associated with higher mitotic activity . D'Errico et al  demonstrated that higher levels of Ki-67 expression in HCC tissue were associated with a higher tumor grade. Nakanishi et al  noted that higher levels of Ki-67 expression were associated with early disease recurrence.
Insufficient apoptosis has been associated with the development and progression of liver tumors.  In HCC, the balance between death and survival is mainly disrupted due to the overactivation of antiapoptotic signals. Therefore, liver cancer cells might express stronger requirements of these intracellular pathways to survive.
Our study results are in accordance with Trerotoli et al  who found that stronger staining was associated with a smaller HCC. They speculated that the higher ratio in smaller rather than larger hepatic nodules, suggests that SCCA is produced and released at different times, likely during the earlier events in HCC progression.
There are several limitations to our study. This is a historical study. Due to the retrospective nature of our study, variable treatment modalities of HCC were included. The patients' cohort was composed of only 61 patients. The group size became even smaller when divided by the SCCA positive and negative staining. Nonetheless, the multiple logistic regression model was applied to assess parameters independently associated with SCCA. The ROC curve was drawn and the C parameter used to quantify the predictive ability of the final regression model.
Up to 40% of all HCC's do not produce AFP . In our study, 70.7% of the specimens did not stain for AFP. No significant correlation was detected between the serum level of AFP, AFP staining and SCCA staining.
Our study results support an invasive diagnostic approach for a suspected malignant hepatic lesion since the SCCA expression in the lesion might provide important information regarding patient prognosis. We feel that if only imaging studies are performed in cirrhotic patients with a suspicious hepatic lesion, valuable prognostic information might be missed.