BACKGROUND: Porokeratosis is a rare group of disorders of epidermal keratinization which is histologically characterized by the presence of cornoid lamella. The malignant potential of porokeratotic lesions is well recognized. Recently, frequent p53 overexpression has been reported and might be related to the carcinogenic potential of porokeratosis. OBJECTIVE: To compare previous foreign results of p53 overexpression in porokeratosis with Korean cases, we studied 24 Korean cases of porokeratosis(7 of Porokeratosis of Mibelli, 14 of DSAP, 2 of Linear Porokeratosis, and 1 of PPPD). METHODS: Immunohistochemical staining was done on the paraffin sections using a labelled streptavidin-biotin-peroxidase complex method with primary antibodies against p53 protein and Ki-67. RESULTS: The epidermis central to cornoid lamellae was positive for p53 protein in 15 of the 24 cases. The epidermis beneath the cornoid lamellae was positive in 3 of the central positive 15 cases and the peripheral epidermis was positive in 1 of the central positive 15 cases. Staining for Ki-67 antigen was increased above background levels in 9 of 24 specimens. No correlation was detected between p53 protein expression and Ki-67 antigen expression. CONCLUSION: The p53 overexpression was observed in Korean cases of porokeratosis but, the expression rate of p53 in Korean cases of porokeratosis was relative less than previous foreign reports.
Antibodies ; Epidermis ; Ki-67 Antigen* ; Paraffin ; Porokeratosis*

Ki-67 has an important application value in clinical practice. However, it is still a little tough in clinical application because of the debate on the cut-off definition of Ki-67 index. This review summarizes most studies on the prognostic and predictive value of Ki-67, analyzes the reasons for the discrepancies among the studies cited, and presents the necessity and clinical significance of scientifically defining the cut-off of Ki-67 index, providing a theoretical basis for Ki-67 in clinical application.
Breast Neoplasms ; diagnosis ; Humans ; Ki-67 Antigen ; analysis ; Prognosis

OBJECTIVE: In this study, we investigated the relationship between the histologic grading of meningiomas and proliferative potentials determined by the Ki-67, proliferating cell nuclear antigen(PCNA) and flow cytometry (FCM) with the aim of determining whether these potentials can be used as a parameter to the proliferative activity, in particular of atypical and malignant meningiomas. METHODS: This study consisted of 47 meningiomas(6 malignant, 14 atypical, and random sampled 27 benign meningiomas). By immunohistochemical staining of Ki-67 and PCNA on formalin-fixed, paraffin-embedded sections, the anti-human rabbit polyclonal antibody against Ki-67 antigen and anti-PCNA monoclonal antibody(PC10) scores were counted. FCM was also performed on paraffin-embedded tissue using a selective staining technique for DNA. DNA ploidy, S-phase fraction, and proliferative index(PI)) were determined. RESULTS: The results are summarized as follows; 1) Proliferation rates as assessed by Ki-67 and PCNA closely correlated with the degree of anaplastic histologic features. 2) Proliferative potentials determined by FCM(S-phase fraction and PI) were not able to distinguish between benign and atypical/malignant meningiomas. 3) DNA ploidy was not a useful indicator of histologic grade in these tumors. 4) Proliferative potentials such as Ki-67 staining index(SI) and PCNA SI did not correlate with the ploidy pattern. 5) There was a linear correlation between Ki-67 SI and PCNA SI, but we could not find a correlation between Ki-67 SI and S-phase fraction or PI. Our results also did not show a statistically signficant correlation between PCNA SI and S-phse fraction or PI. CONCLUSIONS: We conclude that evaluation of the proliferative potentials with Ki-67 and PCNA is important as an additional factor for the prediction of malignancy in meningiomas. A dual study of Ki-67 and PCNA SIs on the same tissue might improve the accuracy with which the proliferative potential of a tumor can be predicted. We demonstrated that FCM in meningiomas is not valuable in predicting the behavior of these neoplasms, but we did observe a trend toward more malignancy with higher percent S-phase fraction and higher PI. Analysis of the S-phase fraction and PI might therefore be a useful tool to discriminate among histologic grades of meningiomas.
DNA ; Flow Cytometry* ; Ki-67 Antigen ; Meningioma* ; Ploidies ; Proliferating Cell Nuclear Antigen*

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8⁺T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.
B7-H1 Antigen/metabolism* ; Humans ; Ki-67 Antigen ; Prognosis ; Recurrence ; Triple Negative Breast Neoplasms/surgery*

In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P < 0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P < 0.05). No significant difference in the Pin1 expression was found between disease stages (FIGO), pathological grades or pelvic lymph node metastasis status (P > 0.05). The expression of Pin1 was significantly higher in adenocarcinoma than in squamous carcinoma of the uterine cervix (P < 0.05). In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P < 0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.
Cervical Intraepithelial Neoplasia/metabolism ; Ki-67 Antigen/*biosynthesis ; Ki-67 Antigen/genetics ; Peptidylprolyl Isomerase/*biosynthesis ; Peptidylprolyl Isomerase/genetics ; Tumor Markers, Biological ; Uterine Cervical Neoplasms/*metabolism

PURPOSE: This study was performed to evaluate the relationship of the expressions of clusterin with Ki-67 and the clinicopathological factors and significance of clusterin expression in human renal cell carcinoma (RCC). MATERIALS AND METHODS: Normal kidney (n=26) and RCC tissues (n=111) were obtained from 111 patients who had undergone a radical or partial nephrectomy. The expressions of clusterin and Ki-67 protein were analysed using immunohistochemical staining. The medical records of the patients were retrospectively reviewed to evaluate the clinicopathological factors. RESULTS: In contrast to the clusterin and Ki-67 expressions of 30.8 and 11.5%, respectively in the normal kidney (n=26), those in the RCC tissues were 93.7 and 28.8% (n=111), respectively (p<0.05). In contrast to the normal tissues, Ki-67 staining was significantly correlated with the expression of clusterin in the RCC tissues (p<0.05). The expression level of clusterin protein in the RCC tissues was significantly related to the tumor stage and grade (p<0.05), but not to age, gender or histological cell type (p>0.05). Furthermore, the recurrence-free survival in patients with strong clusterin expression was significantly lower than in those with weak expression (p<0.05). CONCLUSIONS: These findings suggest that clusterin may be involved in the progression of RCC and; therefore, a useful prognostic variable in patients with an RCC.
Carcinoma, Renal Cell* ; Clusterin* ; Humans* ; Ki-67 Antigen ; Kidney ; Medical Records ; Nephrectomy ; Retrospective Studies

The evaluation of the proliferative potential of malignant neoplasm is of major interest for predicting their biological behavior. MIB-1, a monoclonal antibody against the Ki-67 antigen, is a marker of cell proliferation, which is widely applied to human cancers recently. To assess the growth potential of uterine endometrial carcinoma, we performed immunohistochemical staining of MIB-1 in 34 cases of endometrial adenocarcinoma (endometroid type) from the paraffin sections. We evaluated its correlation with p53 overexpression and known prognostic factors including FIGO grade, nuclear grade, myometrial invasion, and estrogen and progesterone receptors. As a result, the MIB-1 labelling index was significantly correlated with FIGO grade, nuclear grade and myometrial invasion (p<0.05) and there was no significant correlation between MIB-1, ER or PR status. The expression of p53 protein showed significant correlation with FIGO grade and nuclear grade (p<0.05) and there was no significant correlation among p53 protein, myometrial invasion, ER and PR status. The MIB-1 labelling index revealed striking difference between p53 positive and p53 negative group (p<0.05). We concluded that MIB-1 labelling index is associated with poor prognostic parameter in endometrial adenocarcinoma, and may be a useful marker for predicting tumor of high grade and deep myometrial invasion, if MIB-1 labelling index is more than 50% and is accompanied by p53 overexpression.
Adenocarcinoma* ; Cell Proliferation ; Endometrial Neoplasms ; Estrogens ; Female ; Humans ; Ki-67 Antigen ; Paraffin ; Receptors, Progesterone ; Strikes, Employee

Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma. We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively. However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.
Adenoma ; Carcinogenesis ; Colorectal Neoplasms* ; Immune Sera ; Ki-67 Antigen ; Mucous Membrane ; Oncogenes

BACKGROUND: An ovarian surface epithelial tumor is a heterogenous disease, and various biological and molecular factors are important for its development and progression. Several findings support EGFR or c-erbB-2 as adverse prognostic indicators for an ovarian carcinoma. METHODS: We reviewed the histological and clinical findings of 52 carcinomas (17 endometrioid, 16 serous, 13 mucinous and 6 clear cell tumors), and 26 borderline (10 serous and 16 mucinous) tumors. Expression of c-erbB-2, EGFR, p53, and Ki-67 was evaluated on paraffinembedded tissue from a primary ovarian tumor by immunohistochemical methods. RESULTS: Expression of c-erbB-2 was found in 7.6% of tumors and expression of EGFR was found in 9.6% of tumors by immunohistochemical analysis. No significance was found between cerbB- 2 and EGFR expression as indicators of a poor prognosis. The expression of p53 and Ki-67 (>50%) correlated with the grade and type of tumor in the ovarian cancers. p53 and Ki- 67 overexpression (>50%) was absent in the borderline ovarian tumors, whereas ovarian carcinomas showed expression of both p53 and Ki-67. CONCLUSION: Expression of c-erbB- 2, EGFR, p53, and Ki-67 as determined by immunohistochemical analysis did not correlate with prognostic significance. However, p53 and Ki-67 expression may be used as markers to predict aggressive behavior, and to differentiate between malignant and borderline epithelial ovarian tumors. Further large-scale studies are required to clarify the significance of c-erbB-2 and EGFR expression in ovarian tumors.
Epidermal Growth Factor ; Female ; Ki-67 Antigen ; Mucins ; Ovarian Neoplasms ; Ovary* ; Prognosis ; Tumor Suppressor Protein p53

BACKGROUND: Actinic keratosis is a proliferation of transformed neoplastic keratinocytes that are confined to the epidermis, and is induced by exposure to UV radiation in sunlight. The neoplastic transformation is primarily due to p53 gene mutation. OBJECTIVE: Our purpose was to study the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, Ki-67 expression, and p21 expression in the actinic keratosis. METHODS: We reviewed the histopathologic slides of 21 cases of actinic keratosis. We performed immunoperoxidase staining using monoclonal antibody to p53 protein, Ki-67 antigen, p21 protein on the specimen. We stastically analyzed the correlation among p53 expression, epidermal hyperplasia, and dermal inflammation, Ki-67 expression, and p21 expression. RESULT: We found higher expression of p53 in the actinic keratosis with hyperplastic epidermis but this finding was not stastically siginificant (p=0.233). There was no correlation between the expression level of p53 and the severity of dermal inflammation (p=0.755). The expression level of p53 had the significant positive correlation with the expression level of Ki-67 (p=0.001). There was no correlation between the expression level of p53 and the expression level of p21 (p=0.116). CONCLUSION: We observed that p53 expression had a significant positive correlation to only Ki-67 expression. We suggested that further study would be needed on the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, and p21 expression in actinic keratosis.
Actins* ; Epidermis ; Genes, p53 ; Hyperplasia* ; Inflammation* ; Keratinocytes ; Keratosis, Actinic* ; Ki-67 Antigen ; Sunlight