Monoclonal Ki-67 Research Articles

Immunohistochemical markers of proliferation and vascularisation in preneoplastic bronchial lesions and invasive non-small cell lung cancer

Autofluorescence bronchoscopy (AFB) has been shown to be sensitive to detect preneoplastic lesions in central lung airways system. In early stages of carcinogenesis, up-regulation of cyclooxygenase (COX)-2, Ki67 and/or increased angiogenesis may play a role by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and setting up of the metastatic process. The present study compared the expression of proliferative (COX-2, Ki67 and PCNA) and angiogenic markers (CD34 and NG2) between preneoplastic bronchial squamous dysplasia lesions and invasive squamous cell carcinoma. Biopsies obtained during AFB [preneoplastic lesions: low-grade (lesions up to moderate dysplasia), n=13; high-grade lesions (severe dysplasia), n=12] and surgical specimens (resections of bronchogenic carcinoma, n=11) were stained with COX-2, Ki67, PCNA, CD34 and NG2 monoclonal antibodies. Microvessel density (MVD) was analysed based on anti-CD34 immunostaining. Lesions were positive for COX-2 in 12 out of 25 preneoplastic lesions, and in 10 out of 11 invasive carcinomas (p=0.025). In preneoplastic lesions, the mean percentage of Ki67 positive cells was lower compared to invasive carcinomas (37.4+/-5.8 versus 58.6+/-8.4%, p=0.043). In addition, significant differences in MVD were observed between preneoplastic and NSCLC specimen [35.3 (25.9, 61.9) versus 22.1 (20.1, 32.6), p=0.016]. No differences were observed in the mean percentage of PCNA or NG2 positive cells between preneoplastic lesions and invasive carcinomas. Findings of the present study indicate that increases in COX-2 and Ki67 expression may be associated with the development of bronchogenic carcinomas and possibly with acquisition of an invasive phenotype. In contrast, increased CD34 expression in preneoplastic lesions suggests that increased MVD may represent an early marker of lung carcinogenesis.

Chromosomal imbalances are associated with increased proliferation and might contribute to bone destruction in cholesteatoma

Our aim was to evaluate the copy number alterations of chromosomes 3, 7, 8, and 17 in middle ear cholesteatomas and define the association between the rate of cell proliferation and chromosome number changes. Tissues were obtained from 16 patients. Fluorescence in situ hybridization was performed on tumor imprint preparations. Cell proliferation was characterized with Ki-67 monoclonal antibody on cholesteatoma samples and on postauricular skins as control. Different degrees of aneusomy were found for all chromosomes except for chromosome 3. Chromosome copy number alterations were associated with elevated proliferative rate and related also with the aggressiveness of the lesions. Based on our results, we assume that aneusomy of chromosomes 7, 8, and 17 might play an important role during invasion of the adjacent bony structures of cholesteatoma, as well as associate with increased cell proliferation activity, which might lead to the aggressive behavior of the tissue.

R445 – Expression of Proliferative Markers in Cholesteatoma

Problem Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear altering its growth properties. This epithelium believed to have hyperproliferative properties. Inflammatory stimulation of the underlying connective tissue, as well as an autocrine mechanism, may be responsible for the dysregulation and abnormal proliferative feature of the keratinocytes in cholesteatoma. Methods Comparative investigations were performed to assess the epithelial cell kinetics of cholesteatoma and auditory meatal skin. Monoclonal antibody PCNA and Ki-67 immunohistochemical staining were applied. Results Specimens of cholesteatoma samples (n=30) showed an average PCNA score of 26.6% and an average Ki-67 score of 15.9%. Auditory meatal skin(n=8) revealed an average PCNA score of 8.2% and average Ki-67 score of 4.9%. The results of this study confirm a highly increase in the proliferation rate of cholesteatoma keratinocytes, which had an PCNA score that was 3.24 times higher than the score for keratinocyte of auditory meatal skin and Ki-67 score of cholesteatoma was 3.24 times higher than auditory meatal skin. Conclusion We conclude that cholesteatoma is a hyperproliferative activity and that PCNA and Ki-67 immunohistochemical staining are valuable tool for assessing cell kinetics in cholesteatoma. Significance The cholesteatoma possesses a variable degree of proliferative activities depending on its histologic composition. The formation and accumulation of the keratin due to the continuous epithelial growth probably are important elements in inducing the inflammation.

P32 Clinical and genealogical analysis as first step in examination of patients with endometrial cancer

We aimed at investigating by immunohistochemistry the relationship between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR) receptors in a single institution series of 90 primary untreated endometrial cancer patients. The simultaneous assessment of p53 protein, ki67, and neu protein has been carried out.Immunohistochemistry was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against human COX-2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67 (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c-erbB2/neu.There was no difference in the distribution of COX-2, p53, and neu positive cases according to ER or PR positivity, while the percentage of ki67 positive endometrial tumors was significantly higher in ER negative versus ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive tumors showed a statistically significant association with clinicopathological parameters of better clinical outcome. There was no clear association between COX-2 positivity and any of the clinicopathological features. The percentage of ki67, p53, and neu positive tumors was found to be strictly related to more aggressive features. Only advanced stage of disease was found to be a predictor of poor prognosis (P value = 0.034). None of the biological parameters examined was shown to be associated with patient outcome.We showed that COX-2 expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX-2-mediated activities may follow independent pathways. Our findings provide the rationale to design trials based on the combination of antihormones with inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer.

A Histopathological and Immunohistochemical Study of Cell Proliferative Activity in Epulis Osteoplastica and Epulis Fibrosa

Epulis, a relatively common benign polypoid lesion of the gingiva, may be pathologically classified into several subtypes. Although an epulis is thought to be reactive cell proliferation in the gingiva to various stimuli, the mechanism of pathogenesis is unclear. The present study examined histopathological and immunohistochemical analyses to elucidate the cell proliferation in epulis osteoplastica (n=8) using Ki-67 monoclonal antibody MIB-1 as a marker of proliferation and compared that to cell proliferation in epulis fibrosa (n=8). Epulis osteoplastica consisted of massive, trabecular, or woven bone formation surrounded by a proliferation of fibroblasts and blood vessels with minimal inflammatory cell infiltration under the mucosal squamous epithelium. Scanty osteoblastic lining was observed around the bone. Epulis fibrosa was composed of a proliferation of fibroblasts, collagen fibers, and blood vessels with minimal inflammatory cell infiltration ; no evidence of bone formation was found. Immunohistochemically, positive reactivities for MIB-1 were observed in the fibroblasts of epulis osteoplastica and epulis fibrosa, although positive cell rates were higher in epulis osteoplastica than in epulis fibrosa. The findings suggest that epulis osteoplastica has neoplasm-like characteristics unlike epulis fibrosa.

P3-176: Prognostic factors for patients with advanced and metastatic non small cell lung cancer (NSCLC): classical factors= performans status (PS), gender and extension of disease; new factors= expression of EGFR, p53 and cell proliferation defined by Ki67

The aim of the study was to assess the relation between new factors prognostic (expression of EGFR, p53, cell proliferation defined by the monoclonal antibody Ki67); classical factors prognostic (performans status PS, age, gender, extension of the disease) and survival of patients with non-small cell lung cancer stage III and IV. Patient and Methods: 80 patients were included in this study (male 72 / female 8); the median follow up was 15 months. All tumor samples were formalin-fixed and paraffin-embedded. The expression of p53, EGFR and Ki 67 were assessed with the use of im-munohistochemically (IHC). P53 was assessed in 66 cases, EGFR in 73 cases and cell proliferation defined by the monoclonal antibody Ki67 in 63 cases. The expression of p53 was positive in 20 % of cases, EGFR was positive in 58,7 % of cases and cell proliferation in 40 % of cases. Survival was estimated from the date of first cycle of chemotherapy using median survival and the Kaplan-Meier survival analysis method. for each factor. Tabled 1Median survival (month)pp53 positive5,030,2p53 negative8,2Ki67 positive5,30,5Ki67 negative8,4EGFR positive5,30,5EGFR negative8,2Median survival (months)PPS = 011,810-6PS =14,1PS = 21,6Age less 59 years5,40,9Age > 59 years8,2Female7,50,5Male5N09,70,008N11,3N28,3N35,2 Open table in a new tab At this time of the study, there was no relation between expression of p53, EGFR, cell proliferation defined by ki67 and survival. Correlation between PS, nodes extension and survival is confirmed. Larger and longer follow-up studies may be needed to determine the prognostic role of expression of those new factors in NSCLC.

Correlation between expression of p53, EGFR, cell proliferation defined by Ki67, and survival in stage III/IV non-small cell lung cancer (NSCLC)

21181 Background: The aim of the study was to assess the relation between expression of EGFR, p53, cell proliferation defined by the monoclonal antibody Ki67 and survival of patients with non-small cell lung cancer stage III and IV. Methods: 80 patients were included in this study (male 72 / female 8); the median follow up was 15 months. All tumor samples were formalin-fixed and paraffin-embedded. The expression of p53, EGFR and Ki 67 were assessed with the use of immunohistochemically (IHC). P53 was assessed in 66 cases, EGFR in 73 cases and cell proliferation defined by the monoclonal antibody Ki67 in 63 cases. Results: The expression of p53 was positive in 20 % of cases, EGFR was positive in 58,7 % of cases and cell proliferation in 40 % of cases. Survival was estimated from the date of first cycle of chemotherapy using median survival and the Kaplan-Meier survival analysis method. Conclusion: At this time of the study, there was no relation between expression of p53, EGFR, cell proliferation defined by ki67 and survival. Larger and longer follow-up studies may be needed to determine the prognostic role of expression of those factors in NSCLC. [Table: see text] No significant financial relationships to disclose.

Reversible pulmonary trunk banding III: Assessment of myocardial adaptive mechanisms—contribution of cell proliferation

Rapid ventricular conditioning induced by pulmonary artery banding has been recommended for patients with transposition of the great arteries who have lost the chance for the arterial switch operation or whose systemic (right) ventricle failed after the atrial switch. The present study was designed to experimentally evaluate 2 types of pulmonary artery banding (continuous and intermittent) and verify histologically the changes (hypertrophy or hyperplasia or both) of cardiomyocytes and vascular and interstitial cells from the stimulated ventricle beyond the neonatal period. Twenty-one goats, 30 to 60 days old, were divided into 3 groups, each comprising 7 animals, as follows: control group (no surgical procedure); continuously stimulated group (systolic overload maintained for 96 hours); and intermittently stimulated group (4 periods of 12-hour systolic overload, alternated with a resting period of 12 hours). The animals were then killed for histologic and immunohistochemical analysis of the hearts. Murine monoclonal antibody Ki-67 was used as a proliferation cell marker. Myocardial collagen area fraction was determined by Sirius red staining. For both stimulated groups, a significant increase occurred in right ventricular cardiomyocytes and respective nuclei diameters compared with the controls (P < .05). The number of Ki-67-positive cardiomyocytes and interstitial/vessel cells from the right ventricle was augmented in both trained groups in relation to the left ventricle (P < .05). There was no significant difference in the right ventricular collagen area fraction from both trained groups compared with controls. Irrespective of the shorter training time (periods of overload intercalated with resting), the intermittent stimulation regimen was able to produce a similar training of the subpulmonary ventricle compared with the continuous stimulation regarding mass acquisition, cell hypertrophy, and hyperplasia.

The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis

To study the influence of microwave induced thermo-chemotherapy on high-grade urothelial cell carcinomas. Five groups of each three patients were formed of whom initial biopsies and cystectomy samples were collected. Patients were treated 2 days prior to cystectomy with mitomycin-C (group 1), hyperthermia (group 2) or thermo-chemotherapy (group 3). Group 4 patients had been treated with a cycle of six thermo-chemotherapy treatments prior to cystectomy and group 5 patients served as control (no treatment). Tumour samples were stained with Haematoxylin and Eosin, monoclonal antibody Ki-67 and the monoclonal antibody p53. In six out of the nine patients treated with hyperthermia a decrease in proliferation activity in the tumour was found. Seven out of nine patients treated with hyperthermia showed a decrease in p53 activity. A decrease in proliferation activity and p53 activity illustrate the potential role of thermo-chemotherapy as a promising intravesical treatment.

Rates of Cycling Cells in Cryopreserved Valvular Homograft: A Preliminary Study

Some investigators claim that the viability of cryopreserved human valvular homograft is necessary for the duration of implanted homograft. In this preliminary study, the percentage of cycling cells in cryopreserved valvular homografts was evaluated with the use of monoclonal Ki-67 antibody. Three human aortic valves were harvested from multiorgan donors and cryopreserved. Sections of 5 microm in thickness were stained with monoclonal Ki-67 antibody. The proportion of endothelial cells with Ki-67 positive nuclei was 1.80 +/- 0.20%. No differences in distribution were observed from basal to marginal sites. Few fibroblasts showed Ki-67-immunopositivity (0.10 +/- 0.06%) while the Ki-67 immunostaining was 0.80 +/- 0.20% in myocytes. Our preliminary study shows that cryopreserved valvular homograft cells are not only viable but they also have the potential to replicate. These data can lead to the hypothesis that valvular cells could actively replicate even after implantation, permitting cellular renewal and regeneration of extracellular matrix's components.

Evaluation of RNA Markers for Early Detection of Cervical Neoplasia in Exfoliated Cervical Cells

Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (C(t)) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators.

Nonproliferative epithelial alteration and expression of estrogen receptor and Ki67 in the contralateral breast of women treated with tamoxifen for breast cancer

The aim of study was to evaluate the frequency of nonproliferative epithelial alteration and expression of Ki67 and estrogen receptors (ER) in patients using tamoxifen. Forty-four women were selected who had been taking 20mg of tamoxifen daily for at least 12 months for adjuvant treatment of breast cancer. The women underwent core biopsy in the contralateral breast into an area of highest fibroglandular mammographic density. Fragments were analyzed by immunohistochemistry for monoclonal antibody Ki67 and ER, and histopathologic analysis. It was verified that 82% of the patients presented nonproliferative epithelial alteration, 70% were ER-negative, and all had low Ki67 expression. There was no association between duration of tamoxifen therapy, patient age, mammographic density, and presence of nonproliferative alteration (P>0.05). In conclusion, tamoxifen for more than a year showed a high frequency of nonproliferative epithelial alteration and low expression of Ki67 and ER in the normal breast tissue, consistent with low cell proliferation.

Expression of IGFBP2 in Gastric Carcinoma and Relationship With Clinicopathologic Parameters and Cell Proliferation

The insulin-like growth factor (IGF) axis is a complex system composed of two mitogenic ligands, IGF-I and IGF-II, two receptors, IGF-IR and IGF-IIR, and six binding proteins, IGFBP1 to IGFBP6. The IGFBPs exert their actions through their regulation of IGF bioavailability for IGF receptors. The present study evaluated the correlation between IGFBP2 expression and clinicopathologic parameters and cell proliferation in cancer by using surgically resected tissue specimens from 97 patients with gastric carcinoma treated at our hospital. Immunohistochemical staining was performed using IGFBP2 and Ki-67 monoclonal antibody. An obvious difference existed in the IGFBP2 expression between carcinomas and normal mucosa. Correlation between IGFBP2 expression and the depth of penetration, lymph node metastasis, and clinical stage were observed. There was positive correlation between IGFBP2 expression and Ki-67 expression. We conclude that IGFBP2 may be involved in carcinogenesis and progression of gastric carcinoma by promoting cell proliferation.

Effects of low-dose tamoxifen on breast cancer biomarkers Ki-67, estrogen and progesterone receptors

Breast carcinoma is the most common malignancy among women and it has a major impact on mortality. Studies of primary chemoprevention with tamoxifen have generated high expectations and considerable success rates. The efficacy of lower doses of tamoxifen is similar to that seen with a standard dose of the drug, and there has been a reduction in healthcare costs and side effects.The immune reaction to monoclonal antibody Ki-67 (MIB-1) and the expression of estrogen receptors (1D5) and progesterone receptors (PgR 636) in breast carcinoma were studied in patients treated with 10 mg of tamoxifen for a period of 14 days.A prospective randomized clinical trial was conducted with 38 patients divided into two groups: Group A: N = 20 (control group-without medication) and Group B: N = 18 (tamoxifen/10 mg/day for 14 days). All patients signed an informed consent term previously approved by both institutions. Patients underwent incisional biopsy before treatment and 14 days later a tumor tissue sample was obtained during surgical treatment. Positivity was quantitatively assessed, counting at least 1.000 cells per slide. For statistical data analysis, a Wilcoxon non-parametric test was used, and α was set at 5%.Both groups (A and B) were considered homogeneous regarding control variables. In Group A (control), there was no statistically significant reduction in Ki-67 (MIB-1) (p = 0.627), estrogen receptor (1D5) (p = 0.296) and progesterone receptor positivity (PgR 636) (p = 0.381).In Group B (tamoxifen 10 mg/day), the mean percentage of nuclei stained by Ki-67 (MIB-1) was 24.69% before and 10.43% after tamoxifen treatment. Mean percentage of nuclei stained by estrogen receptor (1D5) was 59.53% before and 25.99% after tamoxifen treatment. Mean percentage of nuclei stained by progesterone receptor (PgR 636), was 59.34 before and 29.59% after tamoxifen treatment. A statistically significant reduction was found with the three markers (p < 0.001).Tamoxifen significantly reduced monoclonal antibody Ki-67 (MIB-1), estrogen receptor (1D5) and progesterone receptor positivity (PgR 636) in the breast epithelium of carcinoma patients treated with a 10 mg dose of tamoxifen for 14 days.

Expression of transforming acidic coiled‐coil containing protein 3 is a novel independent prognostic marker in non‐small cell lung cancer

Transforming acidic coiled-coil containing protein 3 (TACC3) is known to be involved in the control of normal cell growth and differentiation and in mechanisms of unregulated growth leading to tumorigenesis. The aim of the present paper was to determine the rate of TACC3 expression in a non-small cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters. A total of 163 NSCLC were analyzed immunohistochemically using a polyclonal TACC3 antibody and monoclonal p53 and Ki-67 antibodies on NSCLC tissue microarrays. A high level of TACC3 expression was observed in 14.8% of cases, preferentially squamous cell carcinomas. Patients whose tumors had a high TACC3 expression had a significantly shorter median survival time. In the Cox regression-based multivariate analysis, TACC3 expression proved to be an independent prognostic parameter (P = 0.031). TACC3 expression was correlated with p53 expression, and patient whose tumors highly expressed TACC3 and p53 had a significantly poorer prognosis than patients whose tumors had low-level expression for both immunostainings (P = 0.006). It is suggested that increase in TACC3 may impart a proliferative advantage to NSCLC and contribute to tumor progression, and that TACC3 expression is a strong prognostic indicator of clinical outcome in NSCLC.

Survivin and MKI67 mRNA Expression in Bladder Washings of Patients with Superficial Urothelial Cell Carcinoma Correlate with Tumor Stage and Grade but Do Not Predict Tumor Recurrence

Seventy percent of patients with superficial urothelial cell carcinoma develop recurrences after transurethral resection of the primary tumor. Because recurrence prediction on the basis of tumor size, grade, and multiplicity is unreliable, all patients need regular bladder examination with cystoscopy. An accurate method to differentiate between patients with short or long recurrence-free periods might reduce the number of invasive cystoscopies in a subgroup of patients. The gene MKI67 (proliferation marker antigen identified by the monoclonal antibody Ki-67) and the antiapoptosis gene survivin are promising prognostic markers, because increased MKI67 and survivin mRNA concentrations indicate short recurrence-free periods (1)(2)(3)(4). In addition to the presence of survivin mRNA in tumor tissue, we observed a relationship between early tumor recurrence and increased concentrations of survivin mRNA in bladder washings (5). Bladder washings are easily obtained during cystoscopy and generally reflect the molecular biological status of the urothelium (6)(7). To confirm our previous findings regarding survivin and to investigate the recurrence-predictive value of MKI67 mRNA, we collected …

Effect of Proton Pump Inhibitors on Hepatic Regeneration

Introduction: The liver is critical in multiple processes, including the clearance of endogenous compounds, the synthesis of macromolecules, and organ-specific biotransformation processes. Therefore, the liver’s regenerating capacity is of vital importance. Multiple pathways are activated in the complex process that leads to hepatic regeneration. In the present study, we aimed to evaluate the effect of proton pump inhibitors omeprozole, lansoprazole, and pantoprazole on hepatic regeneration following partial hepatectomy. Materials and Methods: Four groups were formed with 32 rats in each. Partial liver resections were performed for all animals. Omeprazole (71.4 µg/day), lansoprazole (107 µg/day), pantoprazole (143 µg/day) and placebo (0.5 cm³) were administered to the groups respectively. A quarter of the rats in each group were sacrificed on the 1st postoperative day. The rest were sacrificed on the 3rd, 5th and 7th postoperative days. The remnant regenerating liver mass was removed and weighed, and Ki-67 monoclonal antibody levels were measured. Results: There was no statistical difference between the four groups on the first day in evaluating the weight of the liver mass (p = 0.09) and Ki-67 (p = 0.268) levels. Only the omeprazole group showed a difference; the Ki-67 level was lower in the omeprazole group on the 3rd (p = 0.003, p = 0.0001, p = 0.003), 5th (p = 0.017, p = 0.001, p = 0.0001) and 7th (p = 0.0001) days compared to the other groups. Also the weight of the remnant liver mass was lower in the omeprazole group on the 3rd, 5th and 7th (p = 0.0001) days. Conclusion: We figured out that lansoprazole and pantoprazole have no effects on liver regeneration, whereas omeprazole showed a negative effect on hepatic regeneration.

The prognostic importance of proliferative activity and oestrogen receptor expression in stage I endometrial carcinomas

SummaryThe purpose of this study was to evaluate the prognostic significance of steroid hormone receptor proliferation index in endometrial adenocarcinoma. In this study, the correlation between oestrogen receptor expression, proliferation index and FIGO grade, age, myometrial invasion, tumour size and menopause status was evaluated in 40 patients with endometrial carcinoma. For this purpose, all tumours were stained immunohistochemically with oestrogen receptor and Ki-67 monoclonal antibodies. Oestrogen receptor expression and proliferation indices were found to be statistically associated with grade, age, menopausal status, vascular invasion and tumour size ( p < 0.001). Quantitative assessment of tumour proliferation and expression of oestrogen receptor were found to be important prognostic indicators in endometrial adenocarcinoma.

Ki-67 Proliferative Marker in Lymph Node Aspirates of Patients with Non-Hodgkin's Lymphoma

Proliferative activity of lymphoma cells was tested by immunocytochemical staining with Ki-67 monoclonal antibody in 63 aspirates of peripheral lymph nodes sampled from patients suffering from non-Hodgkin's lymphoma. Referring to the dominant cell population in nodal aspirates, a rising trend of Ki-67 proliferative marker was noted from the small cells (X = 13.20) and small cells with notched nucleus (X = 43.52) and large cells (X = 79.47) with histopathologic equivalents corresponding to aggressive lymphoma. Statistical testing of the difference in the Ki-67 proliferative marker against demographic and clinical-laboratory characteristics of the studied patients revealed the levels of significance for the performance status, bone marrow infiltration, and albumin serum value. Correlation of cytomorphological and immunocytochemical results was tested against International Prognostic Index (IPI). Statistically significant correlation of Ki-67 with cytomorphology and REAL-immunocytochemical classification of lymphoma was confirmed, but not with the IPI index. In order to determine the prognostic importance of Ki-67 marker, the patients were classified into those with low Ki-67 (<20% of proliferating cells), mean proliferation index Ki-67 (range 20-59%), and high proliferative index Ki-67 (positive in over 60% of lymphoma cells). Testing Ki-67 with survival we have found that the low proliferative index was associated with the longest survival, median about 36 mo; for proliferative marker values ranging between 20 and 59%, the median survival was 30.4 mo; and survival of patients with the high proliferative index was only 12.9 mo.

Expression of Proliferation Markers in Human Pituitary Incidentalomas

This study aimed to immunohistochemically assess the proliferation activity of pituitary incidentalomas. A series of 52 incidentalomas studied included 22 gonadotroph cell adenomas, 21 null cell adenomas, and 9 clinically silent adenomas (identified as functioning by immunohistochemistry). We also analyzed the differences in proliferation activity between 43 non-functioning pituitary incidentalomas (not including 9 silent adenomas), and 43 symptomatic non-functioning adenomas (NFAs) that caused visual disturbance. Cell proliferation markers were immunostained using monoclonal Ki-67 (MIB-1) antibody and monoclonal anti-topoisomerase II alpha (Topo-II alpha) antibody. The average of MIB-1 labeling indices in pituitary incidentalomas was 0.61% +/- 0.06%. Overall, both MIB-1 and Topo-II alpha labeling indices of the incidentalomas were significantly lower than those of symptomatic NFAs. There were no significant differences in immunopositivity between the two groups based on gender, age, or subtype. The MIB-1 index of the smallest adenoma group in pituitary incidentalomas was significantly lower than in symptomatic NFAs, while the Topo-II alpha incidentaloma was significantly lower than in symptomatic NFAs. Our findings suggest that small or less invasive pituitary incidentalomas should be observed with follow-up MRI. Large or invasive incidentalomas should be surgically treated if the patients show visual disturbances, hypopituitarism, or pituitary apoplexy during the follow-up period.