Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy in patients with stage IB carcinoma of the cervix

OBJECTIVES: This study was undertaken to evaluate the expression of p53, Ki-67, and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in patients with stage IB squamous cell carcinoma of the cervix, as an attempt to use these proteins as possible markers for residual tumor in cervical cancer. METHODS: Thirty patients with stage IB squamous cell carcinoma of the cervix were submitted to radical hysterectomy (study group), and thirty patients with uterine myoma were submitted to vaginal hysterectomy (control group) and were prospectively studied from November 2001 to September 2002. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological examination showed tumor involvement were excluded from the study. RESULTS: Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal margins of radical hysterectomy in patients with cervical carcinoma compared to the vaginal margins of control patients. This association was demonstrated for p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no difference in p53, Ki-67, and CD31 expression between the proximal and distal regions of the vaginal margins in patients with carcinoma of the cervix. CONCLUSION: The expressions of p53, Ki-67, and CD31 were significantly higher in both the histologically positive (cervical tumor) and negative (vaginal margins) tissues of patients who had undergone radical hysterectomy for cervical cancer compared to the benign control tissues.     

A comparative analysis of human papillomavirus types 16 and 18 and expression of p53 gene and Ki-67 in cervical,vaginal, and vulvar carcinomas

This study aimed to investigate the correlation between HPV positivity, p53 overexpression, and cell proliferative activity in cervical, vaginal, and vulvar squamous cell carcinoma. METHODS: Sixteen vaginal and 31 vulvar squamous cell carcinomas were examined retrospectively for overexpression of p53 gene and Ki67 antigen by immunohistochemistry and for the presence of HPV types 16 and 18 DNA using a polymerase chain reaction (PCR) method. The results were compared with those obtained from 40 cervical squamous cell carcinomas. RESULTS: HPV type 16 or 18 DNA was detected in 21 (52.8%) of 40 cases of cervical carcinomas and p53 overexpression in one (2.5%), while HPV DNA sequences were detected in seven (43.7%) of 16 cases of vaginal carcinoma and p53 overexpression in three (18.7%). With regard to vulvar carcinoma, HPV was harbored in four (12.8%) of 31 cases and p53 overexpression in 19 (61.2%). These results indicated statistically significant inverse correlations between HPV positivity and p53 overexpression (R = -0.999, P < 0.0001). Overexpression of Ki-67 was detected in 28 (70.0%) of 40, 12 (75.0%) of 16, and 21 (67.7%) of 31, cervical, vaginal, and vulvar carcinomas, respectively. There was no significant difference among the three groups. CONCLUSIONS: In cervical carcinoma, HPV types 16 and 18 might play a common causal role, and in vulvar carcinoma, p53 gene mutations might be a main causal factor for carcinogenesis. Vaginal carcinoma, on the other hand, is considered to have transitional characteristics between cervical and vulvar carcinoma.     

Prognostic value of p53 expression in stage IB1 cervical carcinoma

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.     

Allelic Losses at Chromosome 3p Are Seen in Human Papilloma Virus 16 Associated Transitional Cell Carcinoma of the Cervix

OBJECTIVE: Transitional cell carcinomas (TCCs) of the cervix are rare neoplasms of the female genital tract. Although these tumors display urothelial differentiation, there is controversy regarding their histogenetic relationship to squamous cell carcinomas (SCC) of the cervix versus transitional cell carcinomas of the bladder. METHODS: We performed partial allelotyping of five TCCs of the cervix using 23 polymorphic markers located on chromosomes 3p and 9, which demonstrate frequent and early losses in cervical SCC and urothelial TCC, respectively. Multiplex polymerase chain reaction was used on DNA extracted from archival paraffin-embedded tissue using precise microdissection. Additionally, P53 gene mutation analysis was performed using single-strand confirmation polymorphism (SSCP) and the presence of human papilloma virus (HPV) sequences was analyzed using general and specific (types 16 and 18) primers. RESULTS: General HPV sequences were demonstrated in all cases, but the oncogenic strain HPV 16 was present in only three (60%) of the five tumors; no HPV 18 was detected in any sample. Three of five TCCs, all harboring HPV 16 sequences, demonstrated concurrent allelic losses at several 3p loci (specifically 3p12, 3p14.2 [the FHIT gene locus], 3p21.3, and 3p22-24.2). LOH at a single locus on 9q32-qter was demonstrated in one tumor; no other deletions were seen on chromosome 9. P53 gene mutations in exons 5-8 were absent by SSCP analysis. CONCLUSIONS: The infrequent involvement of chromosome 9 in TCCs of the cervix, along with the concurrent presence of 3p LOH and oncogenic HPV 16 in a subset of tumors, suggests a closer histogenetic relationship of this neoplasm to cervical SCCs rather than urothelial TCCs.     

Papillary Squamous Cell Carcinoma of the Uterine Cervix: Report of a Case with HPV 16 DNA and Brief Review

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is a rare variant of squamous cell carcinoma (SCC). It is characterized by a papillary architecture and markedly atypical epithelium. Invasion and metastasis have been reported. We report a case of PSCC in a 72-year-old woman who subsequently tested positive for HPV 16. To our knowledge, this is the first report of HPV typing in a case of PSCC. Our finding of a high-risk HPV type in PSCC may help explain why PSCC has been reported to have a clinical course similar to that of nonpapillary SCC.     

Stage IIa cervix carcinoma with metastasis to the heart: report of a case with immunohistochemistry, flow cytometry, and virology findings

OBJECTIVE: The aim of this study was to report a stage IIa squamous cell cervix carcinoma with intraperitoneal carcinomatosis and metastasis to the heart in a 50-year-old woman and to study the original tumor for expression of oncogenes and tumor suppressor gene proteins, for DNA ploidy, and for human papillomavirus (HPV) infection. METHODS: Clinical course, histopathology of the original tumor, and autopsy record were rewieved. The original tumor was analyzed for expression of CD44 variant 6, p16, p21, p53, retinoblastoma (Rb), and c-erb-2. DNA flow cytometry was performed on tissue samples from the original tumor and from the heart. Sequences of the HPV genome on cervical and cardiac tissue samples were amplified by polymerase chain reaction. RESULTS: Immunohistochemical analysis showed expression of CD44v6 and p16. No expression of p21, Rb, c-erb-B2, and p53 was seen. DNA flow cytometry of the original cervical tumor showed a DNA index (DI) of 1.0. DNA flow cytometry of tissue samples from the posterior wall and from the right ventricle of the heart showed two different aneuploid cell populations with DI of 1.6 and 2.2, respectively. HPV gene sequences were identified neither in the original tumor nor in the heart. CONCLUSIONS: To our knowledge, this is the first case of cervix carcinoma with metastasis to the heart with immunohistochemistry, flow cytometry, and virology findings.     

Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical study of 54 cases

OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras expression and ploidy in borderline tumors of the ovary by assessing their frequency, and relationship to histologic type, tumor recurrence and survival. METHODS: Fifty-four patients with borderline tumors were followed 3-140 months (median: 38 months). Paraffin-embedded sections were stained using monoclonal antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras. The immunohistochemical findings were correlated to histologic subtype, tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24% (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive, Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl-2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases, respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER-2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with ovarian borderline tumors. Further studies to evaluate their prognostic value are warranted.     

Immunohistochemical study of p53 expression in endometrial carcinomas: correlation with markers of proliferating cells and clinicopathologic features

Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase α and Ki-67 monoclonal antibodies, the expression of p53 was studied in 11 normal endometria, 14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to the proliferative activity of the tumors was examined. Normal endometria and simple hyperplasias were completely negative for p53. The PAb1801 indices of complex hyperplasias and complex atypical hyperplasias were 2.5±1.8% and 5.0±3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3 endometrial carcinomas were 10.2±14.2%, 44.4±29/0% and 45.0±32.5%, respectively. These results indicate a progressively enhanced p53 expression in the sequence from normal endometrium, through hyperplasia to carcinoma. A significant correlation between p53 expression and labeling indices of Ki-67 and DNA polymerase α was observed in endometrial carcinomas. The endo-metrial carcinomas with p53 overexpression developed mainly in post-menopausal patients and were frequently high-grade tumors with deep myometrial invasion. These findings may indicate that overexpression of p53 protein contributes to the proliferative activity of the tumor cells.     

Detection of aberrations of chromosome 17 and p53 gene expression and their correlation to histologic grading and prognosis in primary invasive squamous cell carcinoma of the cervix.

We analyzed tumor tissues from 14 patients with invasive squamous cell carcinoma of the cervix for aberrations of chromosome 17 and p53 expression. All but 3 patients were negative for p53 protein expression, the protein being detected in 2 International Federation of Obstetrics and Gynecology stage IIa cancers and 1 stage Ib G3 carcinoma. Significant cytogenetic aberrations in the form of losses and gains of chromosome 17 were diagnosed in 9 and 7 patients, respectively. There was no correlation with tumor prognosis, clinical stage or histologic grade. According to most reports, almost all cervical carcinomas contain integrated human papilloma virus (HPV) and express E6 oncoproteins. Increasing evidence suggests that E6 protein interaction leads to p53 mutation in HPV-infected cervical epithelium. Since most cervical tumors are infected with HPV, and the tumors originate through p53 gene mutation caused by the said interaction, which leads subsequently to the overexpression of p53 oncoprotein, lack of the latter in the remaining 11 cervical tumors may either be the result of technical shortcomings, or the tumor may arise in such circumstances through a p53-independent pathway. On the other hand, 2 of 3 stage IIa cancers and 1 Ib G3 carcinoma were found to be p53 positive, thus supporting the notion that p53 inactivation is a relatively late event in the progression of cervical cancer.     

The role of p53, Bcl-2 and Ki-67 in premalignant cervical lesions and cervical cancer

PURPOSE: The aim of this study was to determine the role of p53, Bcl-2 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 63 patients with a diagnosis of normal squamous epithelium (22 cases), CIN I (14), CIN II (5), CIN III (8) and squamous cell carcinoma (14) were evaluated immunohistochemically for the expression of p53, Bcl-2 and Ki-67 in paraffin sections. RESULTS: The expression of p53 and Ki-67 increased proportionally to the grade of CIN and cervical cancer, but only the increase of p53 expression was statistically significant (p = 0.002). There was no significant correlation between Bcl-2 expression and premalignant and malignant cervical lesions. CONCLUSION: p53 expression may have a role in the carcinogenesis of squamous cell cervical carcinoma whereas Bcl-2 expression has no role. Ki-67 expression can not be used in determining the aggressiveness of CIN lesions.     

Expression of topoisomerase IIalpha,Ki-67, proliferating cell nuclear antigen,p53, and argyrophilic nucleolar organizer regions in vulvar squamous lesions

OBJECTIVE: It was the aim of this study to investigate the expression of topoisomerase IIalpha (topo IIalpha), Ki-67, proliferating cell nuclear antigen (PCNA), p53, and argyrophilic nucleolar organizer region (AgNOR) staining in normal vulvar epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), vulvar intraepithelial neoplasia (VIN, N = 26), as well as squamous cell carcinomas (SCC, N = 22) of the vulva. METHODS: Formalin-fixed, paraffin-embedded archival tissue sections were immunostained with monoclonal antibodies against topo IIalpha, p53, and PCNA, as well as an affinity-isolated prediluted ready-to-use Ki-67 antibody using a standard immunohistochemical method, and stained with a colloid silver solution for AgNORs. Immunostaining was quantitated by determining the percentage of positively staining nuclei in each sample to express the labeling indices (LIs) by counting the immunoreactive nuclei in 1000 epithelial cells per case for each antibody. In each specimen 200 nuclei were examined using a x100 oil emersion lens, and the mean number of AgNORs per nucleus (AC) was calculated. RESULTS: The LIs for topo IIalpha, Ki-67, and PCNA as well as ACs increased stepwise from NE to VCs, VIN lesions, and SCCs. In contrast to PCNA LIs and ACs, a consistent correlation in all four groups was found for Ki-67 and topo IIalpha, suggesting that the latter is a proliferation-associated marker in these tissues. p53 expression was seen 8.3% of VCs, 30.8% of VIN lesions, and 54.45% of SCCs. p53 LIs were not correlated with LIs for topo IIalpha or Ki-67 in SCCs. The LIs for topo IIalpha, Ki-67, PCNA, p53, and ACs were not related to tumor progression, FIGO stage, or tumor grade in SCCs. CONCLUSIONS: This study presents topo IIalpha and Ki-67 as useful proliferation-associated markers of vulvar epithelia.     

Immunohistochemical investigation of p-53, C-NEU and EGFR expression in HPV-related epidermoid endometrial carcinoma

Epidermoid carcinoma (PSCC) of the endometrium is a rare form of endometrial cancer that constitutes about 0.1% of all malignant epithelial tumors of the uterus. The diagnosis of PSCC is based on strict criteria and is made in the absence of a glandular component of the tumor. Squamous cell carcinoma of the endometrium should enter the differential diagnosis in postmenopausal patients in the presence of atypical squamous cells in the uterine curettage, while the cervical biopsies are negative for malignancy. The presence of HPV should be investigated as well, so that its pathogenetic relation is clarified. While no significant relation was found to p-53, C-NEU and EGFR expression this investigation must be continued because. HPV may interact with tumor suppressor genes.     

Immunohistochemical characterization of endocervical papillary serous carcinoma

Abstract.   Nofech-Mozes S, Rasty G, Ismiil N, Covens A, Khalifa MA. Immunohistochemical characterization of endocervical papillary serous carcinoma. Int J Gynecol Cancer 2006; 16(Suppl. 1): 286–292.
Endocervical adenocarcinomas are rare and aggressive neoplasms. Papillary serous endocervical adenocarcinomas are the rarest form of endocervical adenocarcinomas. This tumor exhibits morphologic similarities to its counterparts commonly seen in the endometrium, fallopian tubes, ovaries, and peritoneum, which are known to have an aggressive behavior. Because of the rarity of this tumor, little is known about its immunophenotyping. In this study, we included ten cases of papillary serous carcinomas arising from the uterine cervix (PSCC) diagnosed in the absence of a primary endometrial malignancy. We studied their immunohistochemical profile, using a panel of antibodies against Ki67, bcl-2, p53, carcinoembryonic antigen (CEA), and CD10, and compared them to 20 consecutive cases of cervical adenocarcinoma of conventional cell subtypes (CAC) (15 mucinous, 3 adenosquamous, and 2 endometrioid). Immunostaining was recorded semiquantitatively. Patients with PSCC ranged in age from 27 to 79 years (mean = 51.6 ± 19.1), while the conventional cell subtypes control group were 28–90 years old (mean = 47.5 ± 16.9). Only p53 and CEA immunostaining significantly correlated with the PSCC morphology ( P = 0.001 and P = 0.016, respectively) as shown by Cochran–Mantel–Haenszel Statistics (Modified Ridit Scores). PSCC is a distinctive immunophenotypic subtype of endocervical adenocarcinoma with significantly higher p53 and lower CEA reactivity than other more common histologic subtypes.     

Squamous cell carcinoma of the cervix: HPV 16 and DNA ploidy as predictors of survival

In this study, the hypothesis that DNA ploidy and the presence of HPV 16 and HPV 18 DNA affects survival of patients with squamous cell carcinoma of the cervix was tested. Archival paraffin blocks from biopsy and surgical specimens were obtained from 127 women diagnosed in 1977-1984. Determination of DNA ploidy was by flow cytometry and HPV 16 and HPV 18 DNA status by polymerase chain reaction with subsequent dot-blot hybridization. For each patient, age, stage, treatment modality, and 5-year survival were correlated with ploidy and HPV status. HPV 16 DNA was present in 53% of the tumors. HPV 18 was not detected in this population. HPV 16 DNA was found twice as often in Stages IB and IIA than in advanced-stage disease (III and IV). These advanced-stage tumors were more commonly aneuploid. Neither HPV status nor DNA ploidy were predictive of survival for any stage of disease or therapeutic modality.     

Expression of cyclooxygenase-2 in adenocarcinomas of the uterine cervix and its relation to angiogenesis and tumor growth

OBJECTIVE: The purpose of this study was to evaluate cyclooxygenase (COX)-2 expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and tumor growth. METHODS: Thirty-nine cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-COX-2. Microvessels were immunohistochemically labeled with an antibody to CD34. Computerized image analysis was used to evaluate microvessel density (MVD). The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67 antibody. RESULTS: Twenty-eight tumors (71.8%) were classified as COX-2 positive. COX-2 expression correlated with FIGO stage (P < 0.01). Tumors expressing COX-2 had a significantly higher MVD and Ki-67 index than those that did not express COX-2 (P < 0.05). However, COX-2 expression did not correlate with the apoptotic index. In univariate long-rank analysis, COX-2 expression, MVD, and FIGO stage were associated with shortened survival. However, FIGO stage and MVD were the only independent prognostic factors by multivariate analysis. CONCLUSIONS: Our results suggest that COX-2 expression in cervical adenocarcinomas may contribute to tumor progression by increasing angiogenesis and cell proliferation.     

Well-differentiated villoglandular adenocarcinoma of the uterine cervix: oncogene/tumor suppressor gene alterations and human papillomavirus genotyping.

Twelve well-differentiated villoglandular adenocarcinomas (WDVAs) of the uterine cervix were retrospectively analyzed for the presence and specific genotype of human papillomavirus (HPV), tumor suppressor loss (p53, MCC, APC, BRCA1), cancer gene mutation (K-ras-2, exons 1 and 2, p53 exons 5 to 8), and oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic evaluation was obtained by microdissection, using 4-micron-thick histology sections of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific oligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequence analysis. Tumor suppressor gene loss and oncogene amplification were performed by allelic imbalance analysis in informative subjects based on DNA sequence and microsatellite-length polymorphisms. HPV was present in all tumors and consisted of type 16 (n = 5, 42%) and type 18 (n = 7, 58%) strains, which have been closely associated with cervical neoplasia. K-ras-2 and p53 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV in all 12 tumors supports the role of HPV infection in the molecular pathogenesis of this uncommon neoplasm. The absence of associated oncogene or tumor suppressor gene damage is consistent with indolent biological behavior and the favorable prognosis of this unusual tumor.     

Establishment and Characterization of a New HPV-Negative Squamous Cell Carcinoma Cell Line (Yumoto) from the Human Uterine Cervix

A new cell line, Yumoto, derived from a squamous cell carcinoma of the uterine cervix, was established from serially transplanted tumor tissues in nude mice. Monolayer cultured cells were polygonal and formed pavement-like sheet. They showed a piling-up tendency and were devoid of contact inhibition. Electron micrographs demonstrated the presence of microvilli on the cell surface, abundant tonofilaments in the cytoplasm, and the connection with desmosomes. These electron micrographical characteristics of Yumoto cells were consistent with those of squamous cell origin. Yumoto cells were highly tumorigenic in BALB/c nude mice and produced a well-differentiated squamous cell carcinoma of keratinizing type which closely resembled to the original tumor tissues in nude mice. The presence of HPV DNA was examined using polymerase chain reaction and Southern blot analysis, but no known types of HPV DNA could be detected. Exons 2 through 11 of the p53 gene were analyzed by direct DNA sequencing, revealing a homozygous mutation at codon 281 in exon 8, GAC to CAC (Asp→His). Furthermore, physical p53-gene deletion was demonstrated by dual-color fluorescencein situhybridization. This cell line is useful for studying the carcinogenesis of cervical carcinoma and for investigating the biological characteristics of a HPV-negative and mutated p53 squamous cell carcinoma of the uterine cervix.     

Progression of cervical low grade squamous intraepithelial lesions: in search of prognostic biomarkers

Objective

It has been reported that approximately 10% of low grade squamous intraepithelial lesions (LSIL) progress to high grade squamous intraepithelial lesions (HSIL) within a 2-year follow up. The factors related to lesion progression are currently unknown. The aim of the study was to identify prognostic markers of the course of LSIL. This retrospective study was designed to correlate regression, persistence and progression of biopsy-proven LSIL with patients’ age, HPV genotypes and immunohistochemical expression of the main cell cycle regulating proteins: p53, pRb, p16, and Ki-67.

Study design

A total of 584 consecutive patients with biopsy proven LSIL and 2-year follow-up were included in the age analysis. HPV genotyping was performed in 328 LSIL cases using the SPF10 PCR-LiPA25 (version 1), 238 LSIL cases were immunostained for Ki-67 and p16, and 101 cases were immunostained for pRb and p53.

Results

The odds of LSIL persistence and progression were significantly higher in women 30–39, 40–49 and 50+ years old, as compared to women 20–29 years old (OR 1.89, 2.52 and 2.39, respectively). The odds of persistence and progression were higher in women infected with HPV16, 18, 33 and 52 (OR 3.5, 3.1, 3.5 and 2.9, respectively). There were no significant differences in expression of immunomarkers (p16, p53, pRB and Ki-67) between the lesions that regressed versus the lesions that persisted or progressed.

Conclusions

Patients 30 years of age and older have a higher risk of LSIL progression or persistence as compared to 20–29 year olds. In addition, HPV genotyping, but not the cell cycle markers, may aid in prognosis of LSIL course.     

Comparative studies on the biological significance of the marker for proliferation Ki-67-Antigen and PCNA in primary ovarian carcinoma

OBJECTIVE: It was shown in experimental and clinical investigations, that the biological behavior of malignant tumors is reflected by their proliferative activity. PCNA and Ki-67-Antigen are two nuclear antigens and considered to represent important markers of proliferation. We investigated their proliferation index in primary ovarian carcinomas and correlated the results with tumor stage, grading, histological type and survival. MATERIAL AND METHODS: The expression of PCNA and Ki-67-Antigen was immunohistochemically evaluated using the monoclonal antibodies MIB-1 and PC 10 on formalin-fixed, paraffin-embedded tissue of 49 patients. Statistical data were calculated by means of Fisher's Exact Test and Pearson's Chi 2 Test, survival was estimated by Kaplan Meier Curves. RESULTS: PCNA-expression was shown in all ovarian carcinomas and Ki-67-Antigen-expression was detected with one exception (98%) in all tumors, too. No correlation could be found between Ki-67-Antigen-expression and the prognostic factors mentioned above, whereas a high PCNA-expression was significantly correlated with the tumor grading (G3), (p < 0.05). Patients with ovarian carcinomas with high PCNA proliferation index showed the tendency of a shorter overall survival. DISCUSSION: Ki-67-Antigen and PCNA-expression could be detected in almost all primary ovarian carcinomas. PCNA compared to Ki-67-Antigen is considered to be more useful for the determination of the proliferative activity of ovarian carcinomas, although there was shown just a tendency of overall survival dependent on PCNA-expression, and there was a significant correlation only between PCNA-proliferation index and tumor grading.     

Impact of p53 immunostaining in predicting advanced or recurrent placental site trophoblastic tumors: a study of 12 cases

OBJECTIVES: To identify an indicator that can predict tumor cell spread beyond the uterine corpus. METHODS: We studied clinicopathology and immunohistochemistry of 12 cases of PSTT. Two cases of epithelioid trophoblastic tumor (ETT) were included as reference cases. For immunohistochemistry, antibodies against Ki-67, p53, human chorionic gonadotropin (hCG), human placental lactogen (hPL), carcinoembryonic antigen (CEA, polyclonal antibodies; pCEA), carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), and bcl-2 were used. PSTT cases were divided as confined and non-confined groups (CG and NCG, respectively). CG consisted of stage I cases with no evidence of recurrence during the follow-up, while NCG consisted of either advanced (stage II or higher) or recurrent stage I lesions. RESULTS: Age, the interval from the latest pregnancy, serum hCG/hPL levels, tumor size, mitotic figures, Ki-67 labeling indices, and bcl-2 did not discriminate NCG from CG. CEACAM1 and CEA-related antigens as determined by polyclonal anti-CEA antibodies were specifically stained in PSTT cells, but they could not discriminate groups. p53 was positive in PSTT cells in NCG (6/6, 100%), while it was positive in only one case of CG (1/6, 16.7%), indicating a possible usefulness of p53 immunostaining in predicting an invasive or recurrent propensity of PSTT cells (p=0.015). CONCLUSIONS: This finding also suggests the importance of p53 function in the biology of PSTT cells.