"Immunocytochemical expression of P53, PTEN, FAS (CD95), P16INK4A and HPV L1 major capsid proteins in ThinPrep cervical samples with squamous intraepithelial lesions".

The aim of this study was to further investigate the immunocytochemical expression of p53, PTEN, Fas, p16, and HPV L1 capsid proteins in cervical smears with low and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively). A total of 92 ThinPrep cervical samples, comprising 11 cases of HSIL, 61 cases of LSIL, and 20 negative cases were studied by immunocytochemical methods. The results obtained in LSIL cases were correlated with the available follow up data. Abnormal p53, PTEN, or Fas expression was found in a subset of HSIL cases, while positive expression for p16 was significantly associated with the diagnosis of HSIL (P < 0.0001, P = 0.001, P < 0.0001, and P < 0.0001, respectively). Among cases positive for p16 expression, the staining pattern was weak in 88.9% of LSIL cases and strong in 80% of HSIL cases (P < 0.0001). The p16 negative/L1 positive and p16 positive/L1 negative staining patterns were significantly associated with the presence of LSIL and HSIL, respectively (P < 0.0001). None of these markers had a significant prognostic value in LSIL cases (P > 0.05). Our results suggest that loss of PTEN or Fas expression and p53 overexpression may be involved in the process of neoplastic transformation of the cervical epithelium. Furthermore, negative or weak immunocytochemical staining for p16 in a Pap smear may strongly argue against the presence of a high grade lesion, while the combined p16/L1 staining pattern may be useful as a diagnostic adjunct for differentiating between LSIL and HSIL.

Cytodiagnosis of endometrial carcinoma and hyperplasia on imprint smears with additional immunocytochemistry using Ki-67 and p53 biomarkers.

OBJECTIVE: It is said to be difficult to interpret the different endometrial lesions by cytomorphology; however, evaluation of the microarchitecture of the cell clumps and application of immunocytochemistry can improve diagnostic accuracy. The aim of the present study was to evaluate cytolomorphological features and correlate them with the histological diagnosis of benign and malignant endometrial lesions, and to investigate certain immunocytochemical biomarkers to achieve a more accurate cytodiagnosis. METHODS: In the present study, we graded the cytomorphology on imprint smears of 35 low-grade endometrial endometrioid carcinomas compared with 23 cases of endometrium ranging from disordered proliferative to benign hyperplastic. Additionally, 10 cases of high-grade endometrial carcinoma and 11 cases of atrophic endometrium were evaluated. Ki-67 and p53 biomarkers were applied to the cytological smears. RESULTS: A total cytological score less than six, resulting from nuclear overlapping, nuclear/cytoplasmic ratio, the presence of a branched pattern, vesicular cytoplasm and loss of cohesiveness, distinguished all the cases of disordered proliferative and benign hyperplastic endometrium from low-grade endometrioid carcinomas of endometrium (P < 0.0001). The application of different cut-off values for Ki-67 and p53 helped differentiate certain endometrial lesions in our study. The integration of the immunocytochemical score of Ki-67 and p53 into the cytological score resulted in a final score that was also diagnostically useful. CONCLUSIONS: The results of the present study demonstrated that evaluation of certain cytological features along with specific immunocytochemical findings could improve the accuracy of endometrial cytodiagnosis but our findings need to be tested in a routine clinical situation, using pre-operative cytological samples, to ascertain whether the diagnostic criteria are reproducible.

Prognostic value of EZH2, paxillin expression and DNA ploidy of breast adenocarcinoma: correlation to pathologic predictors.

PURPOSE: The objective of this study was to examine the association of EZH2 and paxillin expression and DNA ploidy status with pathological parameters of breast cancer, aiming to correlate tumor phenotype with its malignant behavior. METHODS: EZH2 and paxillin expression and DNA ploidy were evaluated in imprint smear samples obtained from 105 breast tumors after surgical removal. RESULTS: Increased expression of paxillin was associated with p53 expression (p=0.005), Ki-67 expression (p=0.018) and EZH2 expression (p<0.0001). EZH2 expression correlated with estrogen receptor (ER) and progesterone receptor (PR) status (p=0.01 and p=0.035, respectively), and expression of p53 and Ki-67 (p=0.007 and p<0.0001, respectively). Aneuploid tumors were significantly correlated with poor differentiation (p=0.000), stage of disease (p=0.000), size of the primary tumor (p=0.015), presence of nodal metastasis (p=0.001), ER status (p=0.008), cerbB2 status (p=0.012), and expression of Ki-67 (p=0.001) and EGFR (p=0.018). Multivariate analysis of ploidy results using paxillin and EZH2 expression as dependent variables revealed that aneuploid tumors were associated with disease stage and grade of differentiation, cerbB2 expression and EZH2 expression. CONCLUSION: Our results show that aneuploid tumors, EZH2 expression and paxillin expression correlate with more aggressive phenotype of breast cancer.

Expression of Smad4, E-cadherin and beta-catenin in advanced colorectal cancer: a retrospective study.

PURPOSE: To correlate the expression of E-cadherin and beta-catenin with alterations of expression of Smad4 in advanced colorectal cancer (CRC). METHODS: Tissue specimens from 75 colorectal cancer cases (Dukes stage C and D) were tested for Smad4, E-cadherin and beta-catenin by the Avidin-Biotin immunoperoxidase method. The results were correlated with patients' clinicopathological parameters. RESULTS: Smad4 expression was lost or reduced in roughly 1 out of every 3 Dukes C and D CRCs. Association of Smad4 expression with other clinicopathological parameters was not noted. Association of expression of E-cadherin with other clinicopathological parameters was not noted, apart from tumor location. Expression of beta-catenin was not associated with clinicopathological parameters. Lack of expression of Smad4 was associated with lack of expression of both E-cadherin (<0.000) and beta-catenin (p<0.000). As regards the relation between E-cadherin and beta-catenin, the expression of each seemed to parallel the expression of the other (p<0.000). Beta-catenin was overexpressed in 68.5% of the specimens studied. CONCLUSION: Clinically advanced CRC is associated with a reduced or complete lack of expression of Smad4. Ecadherin and beta-catenin are expressed in parallel with each other and also with Smad4. This tumor suppressor role of Smad4 by affecting both E-cadherin and beta-catenin may indicate a novel pathway for metastatic tumor via cellular reshaping. The precise underlined mechanism(s) and the clinical significance of these findings remain to be determined.

Additional slides from residual ThinPrep Pap tests: Of potential diagnostic benefit in equivocal cases?

The aim of this study was to further evaluate the diagnostic significance of additional slides prepared from residual ThinPrep (TP) Pap Tests. Up to 10 repeat slides were prepared from 105 residual TP cervical samples. All additional slides were evaluated for the presence of diagnostic elements which were not found on the primary TP slide. After the evaluation of the repeat slides, an upgraded diagnosis was noted in 15 cases (14.3%). The reclassified cases included: three negative cases reclassified as two ASC-US and as one LSIL, seven cases of ASC-US reclassified as six LSIL and as one HSIL, and five cases of LSIL reclassified as HSIL. The highest rate (7/15 cases, 46.7%) of cases with an upgraded diagnosis was noted in the ASC-US diagnostic category. Our results suggest that repeat processing of residual TP cervical samples may represent an adjunctive diagnostic tool for a more accurate classification of ASC-US cases. Nevertheless, the practical value of this approach seems to be limited by its significant cost and its uncertain effectiveness.

The value of TOP2A, EZH2 and paxillin expression as markers of aggressive breast cancer: relationship with other prognostic factors.

INTRODUCTION: The immunocytochemical expression of topoisomerase II alpha (TOP2A), enhancer of zeste homologue 2 (EZH2) and paxillin has recently gained increasing attention. Although previous studies have commented on the clinical usefulness of these markers, their role remains controversial. AIM: The purpose of the study was to investigate the expression of TOP2A, EZH2 and paxillin in relation to classic prognostic parameters and their significance as prognostic markers in imprints of resected breast carcinomas. METHODS: Imprint smears from 55 patients who underwent surgical treatment for primary carcinoma in our department between 2005 and 2006 were studied immunocytochemically with the use of TOP2A, EZH2 and paxillin antibodies. RESULTS: The expression of TOP2A correlated with higher histologic grade, tumor size and negative PR expression. High intensity staining for EZH2 expression was associated with higher histologic grade, negative ER and PR expression and positive Ki-67 expression. The expression of paxillin showed no correlation with estrogen/progesterone and HER2 expression nor with tumor grade and stage. CONCLUSION: Our data indicate that TOP2A and EZH2 expression are related to a more aggressive tumor phenotype. The expression of paxillin failed to correlate with any of the studied clinicopathologic factors. Further studies are needed to verify these results.

Repeat processing of residual ThinPrep Pap tests: sampling of the vial may not be invariably homogeneous.

OBJECTIVE: To re-evaluate the reproducibility of additional slides prepared from residual cervical ThinPrep (TP) samples. STUDY DESIGN: Sixty paired specimens (conventional smears and direct-to-vial TP) were studied. Up to 10 additional slides were prepared from each TP vial. All slides were reviewed for adequacy of material, presence of abnormal cells and presence of normal flora or other pathogens. The additional TP slides were further evaluated for the presence of diagnostic elements which were not found on the conventional smear and primary TP slide. RESULTS: Abnormal cells found on the primary TP slide were also identified on all additional slides in 48/50 cases (96%) with squamous cell lesions. The distribution of material on TP slides was evaluated as homogenous in 51 cases (85%) and as non-homogenous in 9 (15%). Using the primary slides (conventional smear and TP) as a reference, additional diagnostic cells upgrading the cytologic diagnosis were found on the repeat slides in 7 cases (11.7%) and fungi consistent with Candida in 3 (5%). CONCLUSION: Repeat processing of residual cervical TP samples may not be an invariably reproducible procedure and the first slide may not be necessarily representative of the specimen as a whole. Nevertheless, both primary and repeat TP slides seem to be extremely effective in detecting a lesion (regardless of grade) in abnormal cases. The exact impact of non-homogeneous sampling of the vial on the diagnostic accuracy of the TP method should be further investigated.

Differential rates of proliferation and apoptosis in nasal polyps correspond to alterations in DNA spatial distribution and nuclear polarization as observed by confocal microscopy.

The study aimed to investigate the expression of p53, Bcl-2 and Ki-67 in relation to the histologic and nuclear qualitative and spatial characteristics of chronic rhinosinusitis with polyposis (CRP). Imprint smears obtained from surgically removed nasal polyps of 20 patients were studied. The polyps were classified according to their histological characteristics as: hyperplasia (simple and pronounced) and squamous metaplasia. The expression of p53, Bcl-2 and Ki-67 was assessed by immunocytochemistry. DNA spatial distribution and nuclear orientation were studied by staining with propidium iodide and examined by confocal microscopy. Positive immunoreaction for p53, Ki-67 and Bcl-2 was observed in 50, 65, and 50% of polyp's smears, respectively. For each diagnosis, the rates were simple hyperplasia 60, 80 and 30%, pronounced hyperplasia 80, 100 and 40%, metaplasia 0, 0 and 100%, respectively. Abnormal chromatin distribution and nuclear disorientation was observed in three cases of pronounced hyperplasia combined with positive immunoreaction for Ki-67 and p53 and negative immunoreaction for Bcl-2. CRP demonstrated different proliferation and apoptotic rates, according to their histology. Nuclear characteristics observed by confocal microscopy are associated with the immunocytochemical markers of proliferation and apoptosis.

Expression of substance P, vasoactive intestinal peptide and heat shock protein 70 in nasal mucosal smears of patients with allergic rhinitis: investigation using a liquid-based method.

OBJECTIVE: The aim of this study was to investigate expression of the neuropeptides substance P, vasoactive intestinal peptide and heat shock protein 70 in the nasal mucosa cells of patients with seasonal allergic rhinitis, in order to obtain more information on the pathophysiological and immunological role of these markers in allergic rhinitis. MATERIAL AND METHODS: Nasal epithelium specimens obtained from 42 patients with allergic rhinitis were studied, using Shandon's Papspin liquid-based cytology method. Smears were immunostained with antibodies against substance P, vasoactive intestinal peptide and heat shock protein 70, and the results were correlated with the clinical features of seasonal allergic rhinitis. RESULTS: A positive reaction for substance P, vasoactive intestinal peptide and heat shock protein 70 was observed in 73.8, 66.7 and 69.0 per cent of the allergic rhinitis mucosal smears, respectively. The Pearson chi-square test showed that 40.5 per cent of the immunostained smears had a positive reaction for one or two of the markers studied (i.e. substance P, vasoactive intestinal peptide or heat shock protein 70), and that 47.6 per cent of the smears had a positive reaction for all the markers (p < 0.0001). CONCLUSIONS: We found a high level of expression of substance P and vasoactive intestinal peptide in the nasal mucosa smears of patients suffering from allergic rhinitis. This indicates a role for these neuropeptides in the neuroregulation of immunity and hypersensivity in this disease. Furthermore, expression of heat shock protein 70 may contribute to the development of allergic rhinitis.

Imprint cytology of vacuum-assisted breast biopsy specimens: a rapid diagnostic tool in non-palpable solid lesions.

OBJECTIVE: Imprint cytology provides a rapid preliminary diagnosis shortly after the completion of breast biopsy. This study aims to assess the validity of imprint cytology for the pre-operative diagnosis of non-palpable mammographic solid lesions excised by vacuum-assisted breast biopsy (VABB). METHODS: Seventy-two women with non-palpable Breast Imaging Reporting and Data System 3 and 4 mammographic solid lesions without microcalcifications underwent VABB on the stereotactic Fischer's table with 11-G Mammotome vacuum probes. Imprint samples were examined (Diff-Quick stain, modified Papanicolaou stain and May-Grünwald-Giemsa). The cores were dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine pathological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated. RESULTS: The sensitivity of the cytological imprints for cancer was 90%. The specificity of the method for cancer diagnosis was 100%. Two precursor lesions were present in the material: one case of atypical ductal hyperplasia, which was successfully detected, and one case of lobular neoplasia, which escaped detection. The cytological imprints were inadequate in four out of 72 cases (5.6%), but none of them were included within the malignant subgroup. CONCLUSIONS: Imprint cytology seems to be an important adjunctive tool in the management of patients with non-palpable mammographic solid lesions. Its very satisfactory sensitivity and optimal specificity could establish its use in general clinical practice.

The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study.

Mutations of the PTEN, p53, and beta-catenin genes are the most frequent molecular defects in endometrial carcinomas. The aim of this study was to investigate their prognostic significance in this form of cancer. Imprint smears were obtained from 80 fresh endometrial tumor specimens and studied immunocytochemically for the expression of PTEN, p53, and beta-catenin proteins. The staining pattern was correlated with several well-established prognostic parameters, including 5-year survival. Positive staining of p53 was significantly correlated with increased stage (P < 0.0001), lymph node metastases (P = 0.001), and a nonendometrioid histology (P = 0.001). On the contrary, positive beta-catenin expression was significantly associated with decreased stage (P = 0.002), decreased grade (P = 0.007), and a negative lymph node status (P = 0.023). PTEN positivity was correlated with decreased stage (P = 0.002) and negative lymph nodes (P = 0.008). All the three markers affected survival significantly in univariate analysis but only beta-catenin had an independent prognostic impact. An independent prognostic significance was also shown for PTEN in the stage I subgroup of patients. The results of our study indicate that loss of beta-catenin expression is a strong and independent predictor of an unfavorable outcome in patients with endometrial carcinoma. Loss of PTEN may also be associated with a worse prognosis in patients with early-stage disease.

Prognostic value of DNA analysis of prostate adenocarcinoma: correlation to clinicopathologic predictors.

The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. DNA ploidy provides important information for the evaluation of the prognosis of prostate cancer. The aim of this study was to investigate the DNA ploidy in imprints from prostate adenocarcinomas in a group of 70 patients in relation to Gleason score, tumor differentiation, stage and PSA serum levels. The DNA content was studied in Feulgen-stained imprint smears through the image analysis technique using a SAMBA 2005 Image analyzer. According to our measurements, a strong correlation was observed between DNA ploidy status and tumor differentiation (p<0.001). A statistically significant difference was found between DNA aneuploidy and increased pretreatment PSA serum levels (>4 ng/ml) (p<0.001), as well as between ploidy pattern and stage of the disease (p<0.001). Our results conclude that DNA ploidy status appears to be an additional marker in the field of prognosis of prostatic adenocarcinoma and could provide useful information on the potential behavior of prostate cancer.

Expression of p120, Ki-67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value.

The cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. The expression of these proteins by immunostaining methods was reported to be of value in determining the prognosis of patients with malignant diseases. In this study, we evaluated the prognostic significance of the expression of nuclear antigens p120, PCNA and Ki-67 in prostate cancer and compared the results with other prognostic factors. Imprint smear samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against p120, Ki-67 and PCNA. The immunostaining results were correlated with Gleason score, tumour differentiation, stage and prostatic specific antigen (PSA) levels. Our findings demonstrate that p120, Ki-67 and PCNA expression in prostatic carcinoma smears, correlated significantly with the degree of Gleason score (P < 0.001). When combining p120, Ki-67 and PCNA positivity with tumour differentiation there was a significant association among these parameters (P < 0.001). Overexpression of p120, Ki-67 and PCNA, was also associated with increased PSA serum levels (>4 ng/ml) (P < 0.001). The distribution of p120, Ki-67 and PCNA expression in prostate carcinomas was not statistically significant for Ki-67 (P = 0.69) and p120 (P = 0.22) but was significant for PCNA (P < 0.001) as far as the histological stage (T2a, T2b, T2c, T3a). P120, Ki-67 and PCNA expression had significant prognostic value for disease-free survival. Our results conclude that nuclear antigens p120, Ki-67 and PCNA appear to be additional markers in the field of prognosis of prostatic carcinoma.

Telomerase expression as a marker in prostate cancer: correlation to clinicopathologic predictors.

The aim of this study was to investigate by an in situ hybridization procedure the Telomerase expression as a marker in prostate cancer and to correlate these results with several prognostic factors concerning this cancer. Imprint smear samples were obtained from 70 prostates removed from patients who underwent radical prostatectomy for prostate adenocarcinoma. Telomerase expression in cancerous prostate smears was studied using an in situ hybridization procedure. The results were correlated with prognostic factors such as pathologic staging, Gleason grading, PSA serum levels and tumour differentiation. Positive Telomerase expression was detected in 88.6% prostate cancer smears. Telomerase expression was significantly correlated with the Gleason score (p < 0.001), tumour differentiation (p < 0.001) and PSA serum levels (p = 0.002). The distribution of Telomerase expression according to histopathological staging was not statistically significant (p < 0.56). In conclusion Telomerase expression could be a marker indicating the malignant potential of prostate cancer.

Diagnostic approach of effusion cytology using computerized image analysis.

The objective of this study is to investigate whether image cytometry is a sensitive and specific method for the differential diagnosis of equivocal cells in routine cytology of effusion smears. One hundred four effusion smears were studied from routine cytologic material. Cytologically 56 (53.8%) of the smears were classified as malignant, 26 (24%) as suspicious and 22 (21.1%) as benign. Two morphometric variables (nuclear major axis length and nuclear area) of the nuclei were measured by an image analysis system. Higher values for the area were found for malignant rather than benign and suspicious cells (p < 0.0005 and p < 0.005 respectively). The same result was extracted for the nuclear major axis length values (p < 0.0005 and p < 0.0005 respectively). Values of nuclear major axis length and nuclear area didn't differ significantly between benign and suspicious cells (p = 0.071 and p = 0.066 respectively). The results show that the range of the values for suspicious cells is closer to the range of the benign cells. Cytomorphometry of the effusion smear cells may provide important information for the differentiation of atypical mesothelial cells from malignant adenocarcinoma cells.

p53 protein expression and oestrogen and progesterone receptor status in invasive ductal breast carcinomas.

p53 protein expression and oestrogen and progesterone receptor status in invasive ductal breast carcinomas The p53 protein expression and oestrogen and progesterone receptors status was investigated in correlation to the grade of malignancy of primary breast carcinomas. Our material constituted imprints from surgical biopsies of 75 invasive ductal breast cancer cases. The p53 protein expression was investigated immunocytologically using the monoclonal antibody p53 DO-7 (DAKO). A biochemical DCC method was applied for the detection of oestrogen and progesterone receptors for all tumours. Fifty-one percent of breast cancer cases were p53 protein positive. A statistically significant association of p53 protein expression and high tumour grade was found (chi2=23.72, d.f.=2, P < 0.001). A statistically significant association was also found between oestrogen and progesterone receptor positive cases and the grade of malignancy (P < 0.001). A negative association between p53 protein expression and oestrogen (ER) and progesterone receptors (PgR) positivity was found. From our results it appears that it is possible to distinguish from grade II tumours two subgroups of cases, one with low malignancy potential and p53 (-), ER (+), PgR (+), and another subgroup with high malignancy potential and phenotype p53 (+), ER (-), PgR (-). The last subset of patients could actually benefit from adjuvant therapy.

Correlations between nuclear/cytoplasmic area ratio and classification of cervical smears.

The aim of this study was to assess the nuclear/cytoplasmic (N/C) ratio using computerized image analysis of cervical smears with intraepithelial neoplasia (CIN) grade I to III associated or not with cellular changes of human papillomavirus (HPV) in an attempt to determine if this method is more sensitive for the estimation of the grade of CIN. One hundred and ten cervical smears from women with a mean age 35.03 years were studied. The cytological diagnosis was as follows: CIN I + HPV (11), CIN II + HPV (11), CIN II + HPV (8), CIN I (7), CIN II (6), CIN III (8), Ca (22), HPV (32), CIN I-II + HPV (2) and CIN II-III + HPV (3). All cases were histologically examined: 93 cases were in agreement and 17 were under- or overestimated cytologically. The morphometric study of cervical smears was carried out by image analysis. Data were analysed by one way analysis of variance followed by Bonferroni test of multiple comparisons. Statistically significant differences were detected between the three grades of CIN or CIN HPV or only HPV (p<0.0001). The results demonstrated that the N/C ratio measured by image analysis on precancerous lesions of cervical smears could be considered as an additional tool for the classification of cervical smears, especially in determining the discrepancies between cytological and histological diagnoses.

p53 protein expression and proliferative activity in ductal breast carcinomas.

The immunocytochemical expression of p53 protein and Ki-67 labelling index in tumour cells of 100 ductal breast carcinomas of different histological grade and stage was evaluated in cytological material. In order to investigate p53 expression and Ki-67 expression an avidin-extravidin immunocytochemical technique was applied to imprints. Monoclonal antibody (MoAb) DO-p53 and proliferating cell monoclonal antibody were used as primary antibodies. A statistically significant difference was observed between p53 protein expression and grade of malignancy and clinical stage (P = 0.001, P < 0.001, respectively). A statistically significant difference was also observed between Ki-67 LI and histological grade and stage of the tumours (P < 0.001, P < 0.001 correspondingly). A correlation was observed between p53 protein expression and Ki-67 LI (P < 0.001). The immunocytochemical study of p53 protein and Ki-67 expression in cytological material represents a simple method which can be applied in routine cytological laboratories for the investigation of potential malignancy of ductal breast cancer.

Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: an immunocytochemical study.

In discriminating benign and malignant origins of cytologically suspicious effusion smears a panel of antibodies against carcinoembryonic antigen (CEA), Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One hundred and thirty seven effusions were studied of which 107 had a malignant and 30 a benign aetiology as determined by clinical and histological examination. Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious. Staining for F was positive in all effusions of benign and 3 of malignant origin. MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of benign origin. Positive CEA was observed in 43% of effusions of malignant origin and in 10 of benign origin. The combination of MOC-31 positivity measured the sensitivity and specificity of the cytological examination in cases where the cytological examination result was suspicious as did F positivity improve the sensitivity for a benign origin of the effusion. Positivity or negativity for CEA is less valuable than the other parameters.

p53 protein expression and proliferative activity in imprints of superficial transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate p53 protein expression and proliferative activity in imprints of tumor biopsies from superficial transitional cell carcinoma of the bladder in relation to the histologic grade of malignancy and recurrence status. STUDY DESIGN: The study group consisted of 70 cases of superficial transitional cell carcinoma of the bladder. In order to investigate p53 protein expression and Ki-67 expression, an immunocytochemical avidin-extravidin complex technique was performed using monoclonal antibodies p53 D0-7 and proliferating cells correspondingly. RESULTS: Thirty-seven percent of superficial transitional cell carcinoma cases showed positive expression of p53 protein. No correlation was found between p53 protein expression and grade of malignancy (P = .45). p53 Protein expression was statistically correlated with a high Ki-67 labeling index (LI) (P < .001) and recurrence status (P < .001). Forty-seven percent of cases showed a Ki-67 LI > 25%. No correlation was found between a high Ki-67 LI and grade of malignancy (P = .703). A significant difference in high Ki-67 LI between recurrent and nonrecurrent tumors of the same grade (P < .001) and between recurrent and nonrecurrent tumors was found independently of grade (P < .001). CONCLUSION: These results on cytologic material could provide useful information on the biologic behavior of superficial transitional cell carcinoma of the bladder at the time of diagnosis.