Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions

BACKGROUND: Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions. METHODS: We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus. RESULTS: The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01). CONCLUSIONS: The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.

The Usefulness of p16INK4a Immunocytochemical Staining in ASC-H Patients

BACKGROUND: The grey zone of cervical cytology, and in particular atypical squamous cells, cannot exclude HSIL (ASC-H) causes diagnostic difficulties and increases medical expenses. We analyzed p16INK4a expression in ASC-H liquid-based cytology specimens (LBCS) to develop more effective methods for the management of ASC-H patients. METHODS: We carried out p16INK4a immunostaining with 57 LBCS of ASC-H diagnostic categories, all of which were histologically cofirmed and 43 cases of which were compared with the results of a human papillomavirus (HPV) chip test. RESULTS: p16INK4a immunostaining with ASC-H LBCS was positive in 20% (3/15) of cervicitis, 25.0% (3/12) of tissue-low-grade squamous intraepithelial lesion, 75.0% (18/24) of tissue-high grade squamous intraepithelial lesion (HSIL), and 100% (6/6) of invasive cancer cases. The positivity of p16INK4a in LBCS was correlated with higher grade of histologic diagnosis (r=0.578, p=0.000). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of p16INK4a immunostaining for the prediction of tissue-HSIL+ were 80.0%, 77.8%, 80.0%, and 77.8%, respectively. The sensitivity, specificity, PPV, and NPV of p16INK4a immunostaining plus HPV chip test for predicting tissue-HSIL+ were 71.2%, 86.4%, 84.2%, and 79.2%. CONCLUSIONS: p16INK4a immunostaining as well as HPV chip testing with remaining LBCS with ASC-H are useful objective markers for the prediction of tissue-HSIL+.

Clinicopathologic Significances of EGFR Expression at Invasive Front of Colorectal Cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is frequently expressed in the invasive front of colorectal cancer (CRC), but its clinicopathologic significance remains unclear. We investigated the clinical value of the EGFR expression at the invasive front of CRC. METHODS: We performed an immunohistochemical analysis in order to examine the expression and distribution of EGFR in 214 cases of CRC. The EGFR status was considered positive when > or =1% of the tumor cells had membranous staining. RESULTS: Overall, an EGFR expression was observed in 144 (67%) cases and it had no significant relationship with the clinicopathologic parameters. However, an EGFR expression at the invasive front was correlated with lymphatic invasion, lymph node metastasis and a high level of serum carcinoembryonic antigen (p = 0.028, p = 0.043, and p = 0.045, respectively). For the budding-positive CRCs liver metastases were found in the cases with an EGFR expression at the budding, but no liver metastasis occurred in the EGFR negative cases at the budding (p = 0.030). CONCLUSIONS: An EGFR expression at the invasive front has clinicopathologic significances in patients with CRC. An EGFR expression at tumor cell budding is a pathologic marker that suggests the high potential for liver metastasis in CRC.