Proliferating Cell Nuclear Antigen Scores Research Articles

Efecto del extracto alcohólico de Tarantula cubensis y el destilado de Nerium oleander sobre los marcadores de proliferación celular en la carcinogénesis de colon

Colorectal Cancer (CRC) is defined as colon and rectum cancer and is among the major causes of mortality in developed Countries. Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander distillate (NOD) are reported to have anticancer and antioxidative activity. In this study, it was aimed to research the impact on cell proliferation markers of TCAE and NOD given simultaneously in experimental colon cancer. A total of 24 rats, 6 in each group, were used in the study. Cancer Control (CC): Azoxymethane was administered at the beginning of the experiment at a dose of 15 miligrams (mg)· kilograms-1 (kg), (Subcutaneous, SC) twice, with an interval of a week (wk), to induce cancer. CC+TCAE: the dosage of Azoxymethane administered was 15 mg·kg-1 (SC) twice a wk at the beginning of the experiment, while in the case of TCAE, it was 0.2 mL·kg-1 (SC) once a wk for 18 wk from the beginning of the experiment. Fifteen mg·kg-1 (SC) of Azoxymethane was administered twice at one-wk intervals at the beginning of the experiment to the CC+NOD group, and NO distillate (NOD) was given with water throughout the experiment. Afterwards, animals were euthanized under appropriate conditions, paraffin blocks formed from colon tissues, histochemical AgNOR (Silver-stained nucleolar organizer regions), and immunohistochemical PCNA (proliferating cell nuclear antigen) stainings were performed. In the study, immunohistochemically, PCNA scores and AgNOR count per nucleus (AgNCI) were significantly decreased in C-TCAE and C-NOD groups (P<0.001). AgNOR Area index (AgNAI) (P<0.01), Core Area Index (CAI) (P<0.05), and AgNOR Area index/Core Area Index (AgNAI/CAI) (P<0.01) scores were significantly decreased in the C-TCAE group. As a result, it was concluded that both TCAE and NOD are effective as chemopreventive drugs and that TCAE presents a more pronounced antiproliferative effect than NOD.

Effects of sclerostin antibody on bone healing.

Promoting bone healing after a fracture has been a frequent subject of research. Recently, sclerostin antibody (Scl-Ab) has been introduced as a new anabolic agent for the treatment of osteoporosis. Scl-Ab activates the canonical Wnt (cWnt)-β-catenin pathway, leading to an increase in bone formation and decrease in bone resorption. Because of its rich osteogenic effects, preclinically, Scl-Ab has shown positive effects on bone healing in rodent models; researchers have reported an increase in bone mass, mechanical strength, histological bone formation, total mineralized callus volume, bone mineral density, neovascularization, proliferating cell nuclear antigen score, and bone morphogenic protein expression at the fracture site after Scl-Ab administration. In addition, in a rat critical-size femoral-defect model, the Scl-Ab-treated group demonstrated a higher bone healing rate. On the other hand, two clinical reports have researched Scl-Ab in bone healing and failed to show positive effects in the femur and tibia. This review discusses why Scl-Ab appears to be effective in animal models of fracture healing and not in clinical cases.

Assessment of proliferating cell nuclear antigen (PCNA) expression at the invading front of oral squamous cell carcinoma

BackgroundAccurate prediction of the behaviour of oral squamous cell carcinoma (OSCC) is necessary to determine prognosis and provide appropriate treatment. Therefore, it is important to investigate potential prognostic markers to determine their predictive ability. Histological assessment of specific features at the invading front of oral squamous cell carcinomas has shown to provide accurate and reproducible prognostic information. Proliferating cell nuclear antigen (PCNA) is a nuclear marker known to reflect cell turnover and may be used as a marker for tumour aggressiveness.MethodsTwenty cases of OSCC were histologically assessed to evaluate the correlation between proliferating cell nuclear antigen expression and invasive front grading. Each case was first assessed on a haematoxylin and eosin stained slide and an invading front grading (IFG) score was determined. In order to obtain a PCNA score, immunohistological staining was carried out using the peroxidase-labelled streptavidin-biotin technique with the monoclonal antibody PC10.ResultsIn all cases, tumour islands had a periphery of intensely stained proliferating cell nuclear antigen-positive epithelial cells. The average IFG score was 8 ± 1.8, and the average PCNA score was 75% ± 11.2. Regression analysis was done using data from the IFG score and PCNA score and taking the latter as the predictor variable. The Pearson correlation coefficient was 0.134, with a p-value of 0.572.ConclusionSince the correlation between PCNA score and IFG score was not significant (p > 0.05), we conclude that there is no association between cell proliferation at the invading tumour front and the histological grading of OSCC.

Immunohistochemical markers: Carcinoembryonic antigen, p53, Ki-67, and proliferating cell nuclear antigen as prognostic factors for colorectal cancer

<p>Introduction. There has been a progressive increase in the frequency of colorectal carcinoma for the last twenty years. In order for a doctor to estimate the life expectancy and/or the treatment of these patients, oncology makes use of prognostic and predictive factors. They are divided into: clinicosurgical, pathohistological and immunohistochemical markers. The aim of this study is to determine the significance of immunohistochemical markers such as carcinoembryonic antigen (CEA), p53, Ki-67 as well as proliferating cell nuclear antigen (PCNA) for predicting survival in patients with colorectal carcinoma. Methods. From 1st January 2010 to 1st December 2017, 484 patients with colorectal carcinoma who underwent analysis of immunohistochemical markers in carcinoma tissue (CEA, p53, Ki-67 and PCNA) were treated in Public Hospital "St Vračevi" in Bijeljina. Results. Immunohistochemical analysis of primary colorectal adenocarcinoma tissue showed a considerably high positive expression level of CEA in 301 (62%) patients, p53 in 329 (68%), PCNA in 314 and Ki-67 in 275 (56.8%) patients. Patients with a high positive expression of CEA, PCNA, and p53 had a statistically lower survival rate, compared to the patients with low CEA, PCNA and p53 expression score. There was no statistically significant difference in the survival of patients with a considerably high immunohistochemical Ki-67 expression score, compared to the ones with low score. Conclusion. Although immunohistochemical markers are useful predictors of survival in these patients, immunohistochemical analysis is not used for the routine examination of colorectal carcinoma.</p>

The Contribution of Histochemical and Immunohistochemical Techniques in Assessing the Proliferative Capacity and Prognosis for Renal Cell Carcinoma

The drive to prolong life and to improve life quality in patients suffering from cancer forms of any kind means that, aside from the necessary treatment, prognostic evaluations are needed. In our present study we included 63 patients with renal cell carcinoma. The histological samples obtained in surgery were studied through the classical histopathology methods, histochemical and immunohistochemical techniques. The histological degree of tumor differentiation was assessed for all cases, falling within all 4 classification grades. The immunohistochemical reaction for PCNA (proliferating cell nuclear antigen) was performed, utilizing the PC 10-LSAB antibody through visualization with the LSAB-DAB kit. This was the method used for assessing the process of tumor proliferation. Subsequently, the histological degree of differentiation was correlated with the PCNA score. We anticipate a reserved prognosis for patients with a positive expression on most tumor cells, which represents a high PCNA score.

Application of Dynamic Contrast-Enhanced MRI in the Therapeutic Evaluation of the Chinese Medicine Kanglaite in Treating Colorectal Cancer

Background: Magnetic resonance imaging (MRI) can provide a reference for tumor treatment and its quantitative parameters can serve as imaging indicators that reflect tumor angiogenesis and vascularity. Kanglaite (KLT) has therapeutic effects on cancers. In this study, DCE-MRI was used to investigate its application in evaluating KLT anti-colorectal cancer. Objectives: Evaluating the efficacy of Kanglaite (KLT) injection for treatment of colorectal cancer with dynamic contrast-enhanced MRI (DCE-MRI) parameters. Methods: This study was an experimental study. The 20 successfully modeled nude mice were randomly assigned to 2 groups: blank control group (n = 10) and the KLT injection group (n = 10). The research protocol was approved by the ethics committee of the second affiliated hospital of Xinjiang medical university (protocol NO: 20140216-12) in 2015. A subcutaneous xenograft colorectal tumor model was subjected to KLT treatment. DCE-MRI obtain the parameters including Ktrans, Ve, Kep, Vp, immunohistochemical staining measure microvascular density (MVD), levels of vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA). Results: Compared to the blank control, the volume of tumor in the KLT group markedly reduced by 49%. 48 hours after, compared to the blank control, the Ktrans (0.028 ± 0.009 vs 0.012 ± 0.006), Ve (0.312 ± 0.089 vs 0.287 ± 0.037), and Kep values (0.321 ± 0.056 vs 0.577 ± 0.033) decreased in KLT group (P < 0.05). In contrast, the Vp value (0.094 ± 0.037 vs 0.043 ± 0.017) was significantly elevated in the KLT group (P < 0.05). There is a correlation between Ktrans, Kep and VEGF score, MVD count, and PCNA score. Conclusions: The parameters of DCE-MRI may be used as imaging biomarkers for assessing the status of tumor-bearing vasculatures and provide a basis for evaluating the efficacy of anti-tumor drugs.

Effect of stem cell application on Asherman syndrome, an experimental rat model.

We evaluate the effect of stem cells to induce endometrial proliferation and angiogenesis on Asherman Syndrome (AS). The experimental study was performed in stemcell research laboratory. Forty Wistar-Albino rats were divided according to groups. In group1 (n = 10) to establish the model; trichloroacetic acid was injected to right uterine horn. Two weeks later, intrauterine synechia was confirmed. In group2 (n = 10), 2weeks later, 2 × 106 mesenchymal stem cells (MSC) were injected into right uterine horn followed by three intraperitoneal injections of MSCs. In group3 (n = 10), daily oral estrogen was initiated on the second week. In group4 (n = 10), MSC injections and oral estrogen was given together. The amount of fibrosis, vascularisation, inflammation and immunohistochemical staining with vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and Ki-67 were evaluated in the uterine tissues. In all treatment groups; fibrosis decreased but vascularisation and immunhistohemical stainings increased in the experimental side. The amount of fibrosis, vascularisation, Ki-67 and PCNA scores were similar between group2 and 3. In group4, comparing to group2, less fibrosis but more Ki-67, PCNA and VEGF staining was observed. Stem cells, when added to estrogen, are a highly effective alternative to induce regeneration of endometrium in Asherman Syndrome therapy.

Acid suppression increases rates of Barrett’s esophagus and esophageal injury in the presence of duodenal reflux

The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.

The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis model.

The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells.

Immunohistochemical Characteristics of Intramural Leiomyomata That Enlarge during Controlled Ovarian Hyperstimulation for in vitro Fertilization

Background/Aims: This study aimed to determine the immunohistochemical characteristics of intramural leiomyomata that enlarged during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Methods: For thisretrospective case-control clinical study and immunohistochemical analysis, 5 patients with enlarged intramural leiomyomata during COH for IVF, who had undergone myomectomy immediately after a failed IVF cycle, were recruited retrospectively. Fifteen consecutive patients who had had myomectomy for intramural leiomyomata <5 cm, but had never undergone any infertility treatment, served as the control group. Histological examinations and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), transforming growth factor-β (TGF-β) and fibronectin were performed on all specimens taken from the study and control groups. The main outcome measures were defined as histological and immunohistochemical scores. Results: Hematoxylin and eosin as well as PCNA staining showed increased mitotic index, cellularity and proliferation index in these growing leiomyomata (study group). There were neither increased mitoses nor cellularity in the leiomyomata of the control group, while PCNA, TGF-β and fibronectin scores in the study group were significantly higher than those in the control group (p < 0.001). Conclusion(s): This study is the first to report increased TGF-β, PCNA, cellularity and mitosis in leiomyomata enlarging during COH for IVF. Further studies with larger sample size are needed to determine the role of TGF-β, PCNA and fibronectin in the growth of leiomyomata during COH.

Recurrence Rate, Clinical Outcome, and Cellular Proliferation: Indices as Prognostic Indicators after Incomplete Surgical Excision of Cutaneous Grade II Mast Cell Tumors: 28 Dogs (1994–2002)

The objectives of this study were to determine local recurrence rate, clinical outcome, and prognostic value of the number of argyrophylic nucleolar organizer regions (AgNORs), presence of proliferating cell nuclear antigen (PCNA), and number of Ki‐67‐positive nuclei after incomplete surgical excision of canine cutaneous grade II mast cell tumors (MCTs). This retrospective study included 30 MCTs in 28 dogs. Medical records were examined and follow‐up information was obtained from owners and referring veterinarians. Only cases in which excision was incomplete and no anvcillary therapy (other than prednisone) for MCT was given were included. Paraffin‐embedded tumor tissues were retrieved for AgNORs, PCNA, and Ki‐67 staining. Median follow‐up time was 811.5 days. Seven (23.3%) tumors recurred locally. Median time to local recurrence was not reached with a mean of 1,713 days. The estimated proportions of tumors that recurred locally at 1,2, and 5 years were 17.3, 22.1, and 33.3%, respectively. Eleven (39.3%) dogs developed MCTs at other cutaneous locations. Median progression‐free survival was 1,044 days. Median overall survival was 1,426 days. The combination of Ki‐67 and PCNA scores was prognostic for local recurrence (P= .03) and development of local recurrence was prognostic for decreased overall survival (P= .04). Results suggest that a minority of incompletely excised MCTs recur. Therefore, ancillary local therapies may not always be necessary. However, local recurrence can negatively affect survival of the affected dogs. Cellular proliferation indices may indicate the likelihood of MCT recurrence after incomplete excision.

Association of argyrophilic nucleolar organizing regions, Ki-67, and proliferating cell nuclear antigen scores with histologic grade and survival in dogs with soft tissue sarcomas: 60 cases (1996—2002)

To determine whether argyrophilic nucleolar organizing regions (AgNORs), Ki-67, and proliferating cell nuclear antigen (PCNA) scores were associated with histologic grade and survival in dogs with soft tissue sarcomas (STSs). Retrospective study. 60 dogs with STSs. Medical records were examined and histologic specimens were reviewed. Tissue specimens obtained from archival materials were used to prepare sections for histologic staining for AgNOR and immunohistochemical staining for Ki-67 and PCNA labeling. Follow-up monitoring was obtained by reevaluation or telephone conversations with referring veterinarians or owners. 27 (45%) STSs were grade 1, 23 (38%) were grade 2, and 10 (17%) were grade 3. The mean and median AgNOR, Ki-67, and PCNA scores were determined, and significant positive associations among AgNOR and Ki-67 scores with histologic grade and mitotic score were detected. Fifty-four dogs had adequate follow-up examinations and were included in survival analysis and evaluation of prognostic factors. Overall median survival time was > 1,306 days. Twelve of 54 (22%) dogs died of tumor-related causes. Metastatic disease developed in 8 of 54 (15%) dogs. Results of univariate analysis indicated that increased mitotic score, increased AgNOR score, increased Ki-67 score, incomplete surgical margins, noncurative intent surgery, Ki-67 score greater than the median Ki-67 score, and AgNOR score greater than the median AgNOR score were prognostic factors for decreased survival time. Results of multivariate analysis indicated that increased AgNOR score was the only prognostic factor for decreased survival time. Results suggested that AgNORs and possibly Ki-67 should be routinely evaluated with histologic grading for STSs in dogs.

Recurrence Rate, Clinical Outcome, and Cellular Proliferation Indices as Prognostic Indicators after Incomplete Surgical Excision of Cutaneous Grade II Mast Cell Tumors: 28 Dogs (1994–2002)

The objectives of this study were to determine local recurrence rate, clinical outcome, and prognostic value of the number of argyrophylic nucleolar organizer regions (AgNORs), presence of proliferating cell nuclear antigen (PCNA), and number of Ki-67-positive nuclei after incomplete surgical excision of canine cutaneous grade II mast cell tumors (MCTs). This retrospective study included 30 MCTs in 28 dogs. Medical records were examined and follow-up information was obtained from owners and referring veterinarians. Only cases in which excision was incomplete and no anvcillary therapy (other than prednisone) for MCT was given were included. Paraffin-embedded tumor tissues were retrieved for AgNORs, PCNA, and Ki-67 staining. Median follow-up time was 811.5 days. Seven (23.3%) tumors recurred locally. Median time to local recurrence was not reached with a mean of 1,713 days. The estimated proportions of tumors that recurred locally at 1, 2, and 5 years were 17.3, 22.1, and 33.3%, respectively. Eleven (39.3%) dogs developed MCTs at other cutaneous locations. Median progression-free survival was 1,044 days. Median overall survival was 1,426 days. The combination of Ki-67 and PCNA scores was prognostic for local recurrence (P = .03) and development of local recurrence was prognostic for decreased overall survival (P = .04). Results suggest that a minority of incompletely excised MCTs recur. Therefore, ancillary local therapies may not always be necessary. However, local recurrence can negatively affect survival of the affected dogs. Cellular proliferation indices may indicate the likelihood of MCT recurrence after incomplete excision.

Canine Mast Cell Tumors: Correlation of Apoptosis and Proliferation Markers with Prognosis

The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it is less useful for grade 2 MCTs because they exhibit considerable variation in biological behavior. In this retrospective study, immunohistochemical staining for Ki‐67, proliferating cell nuclear antigen (PCNA), and survivin and a standardized argyrophilic staining of nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin‐embedded specimens of canine cutaneous MCTs, for which clinical follow‐up data were available. Cox regression models indicated that the Ki‐67 score (hazard ratio, 1.92; P &lt;.001) and mean AgNOR score (hazard ratio, 2.57; P &lt; .001) were significantly associated with Patnaik grade and survival time. A binary Ki‐67 variable (cutoff point Ki‐67 score = 1.8) was a significant predictor of survival for dogs with grade 2 MCTs. The estimated 1‐, 2‐, and 3‐year survival probabilities for dogs with grade 2 MCTs and Ki‐67 scores less than 1.8 were 0.92, 0.86, and 0.77, respectively (SEs, 0.08, 0.14, and 0.23, respectively; median not estimable). The corresponding survival probabilities for dogs with grade 2 MCTs and Ki‐67 scores higher than 1.8 were 0.43, 0.21, and 0.21, respectively (SEs, 0.19, 0.18, and 0.18, respectively; median survival time, 395 days). No significant association was identified between survival and survivin score or PCNA score. This study shows that both mean AgNOR score and Ki‐67 score are prognostic markers for canine MCTs. The Ki‐67 score can be used to divide Patnaik grade 2 MCTs into 2 groups with markedly different expected survival times.

Canine Mast Cell Tumors: Correlation of Apoptosis and Proliferation Markers with Prognosis

The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it is less useful for grade 2 MCTs because they exhibit considerable variation in biological behavior. In this retrospective study, immunohistochemical staining for Ki-67, proliferating cell nuclear antigen (PCNA), and survivin and a standardized argyrophilic staining of nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin-embedded specimens of canine cutaneous MCTs, for which clinical follow-up data were available. Cox regression models indicated that the Ki-67 score (hazard ratio, 1.92; P < .001) and mean AgNOR score (hazard ratio, 2.57; P < .001) were significantly associated with Patnaik grade and survival time. A binary Ki-67 variable (cutoff point Ki-67 score = 1.8) was a significant predictor of survival for dogs with grade 2 MCTs. The estimated 1-, 2-, and 3-year survival probabilities for dogs with grade 2 MCTs and Ki-67 scores less than 1.8 were 0.92, 0.86, and 0.77, respectively (SEs, 0.08, 0.14, and 0.23, respectively; median not estimable). The corresponding survival probabilities for dogs with grade 2 MCTs and Ki-67 scores higher than 1.8 were 0.43, 0.21, and 0.21, respectively (SEs, 0.19, 0.18, and 0.18, respectively; median survival time, 395 days). No significant association was identified between survival and survivin score or PCNA score. This study shows that both mean AgNOR score and Ki-67 score are prognostic markers for canine MCTs. The Ki-67 score can be used to divide Patnaik grade 2 MCTs into 2 groups with markedly different expected survival times.

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma.

To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma. Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion. Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Expression of the proliferating cell nuclear antigen and clinicopathological features in intracranial meningiomas

PC10, a monoclonal antibody (mAb) to proliferating cell nuclear antigen (PCNA) is known to show immunoreactivity in paraffin-embedded specimens. The authors present the relation between PCNA expression and clinicopathological features in 38 intracranial meningiomas. PCNA scores were obtained by immunohistochemical staining of the paraffin-embedded sections using a streptoavidin-biotin immunoperoxidase method with PC10 mAb. Univariate analysis showed that high PC10 scores were associated with old age (≥ 50 years old), male, recurrent tumours, and meningothelial type. However, these high scores did not reach a statistical significance (P> 0.05). PC10 scores of the basal meningioma tended to be higher than that of the hemispheric meningioma (P< 0.05). The staining intensity of PCNA was also markedly increased in basal meningiomas. It is suggested that the proliferative potential is higher in basal meningiomas than in hemispheric meningiomas. Moreover, these results could reflect high recurrence and difficulty in management of the skull base meningiomas.

Proliferating cell nuclear antigen and c‐erbB‐2 oncoprotein expression in adenoid cystic carcinomas of the salivary glands

Background Adenoid cystic carcinoma (ACC) of the salivary gland shows a variable clinical course. It would be helpful to discover reliable biologic markers in the management of patients with ACC. Methods We examined proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein expression on 30 cases of ACC of the salivary glands. The immunohistochemical results, and size, location, and histologic grade of the tumors were compared with the clinical outcome of the patients. Results Mean PCNA positivity of ACCs was 15%, and was higher in solid than in cribriform/tubular areas. High PCNA value was significantly correlated with shorter disease-free and overall survival of the patients with ACC. c-erbB-2 overexpression was observed in only five cases, focally in cribriform/tubular areas. High histologic grade, which was determined by the presence of solid components, showed a trend toward shorter survival. Size and location of ACC were not associated with patient outcome. Conclusions The present study indicates that PCNA score may be one of the most useful prognostic factor of ACC. © 1999 John Wiley & Sons, Inc. Head Neck 21: 414–419, 1999.

Proliferating cell nuclear antigen and c-erbB-2 oncoprotein expression in adenoid cystic carcinomas of the salivary glands

Adenoid cystic carcinoma (ACC) of the salivary gland shows a variable clinical course. It would be helpful to discover reliable biologic markers in the management of patients with ACC. We examined proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein expression on 30 cases of ACC of the salivary glands. The immunohistochemical results, and size, location, and histologic grade of the tumors were compared with the clinical outcome of the patients. Mean PCNA positivity of ACCs was 15%, and was higher in solid than in cribriform/tubular areas. High PCNA value was significantly correlated with shorter disease-free and overall survival of the patients with ACC. c-erbB-2 overexpression was observed in only five cases, focally in cribriform/tubular areas. High histologic grade, which was determined by the presence of solid components, showed a trend toward shorter survival. Size and location of ACC were not associated with patient outcome. The present study indicates that PCNA score may be one of the most useful prognostic factor of ACC.

Immunohistochemically stained markers (p53, PCNA, bcl-2) in dysplastic lesions of the larynx

The percentage of malignant transformation of laryngeal dysplastic lesions is difficult to estimate. There is a need for new histological markers which could enable more objective assessment of the premalignant stages of the larynx and help in estimation of the potential of future neoplastic progression. We performed a retrospective study to determine whether immunohistochemical staining for the proliferating cell nuclear antigen (PCNA), tumour suppressor gene protein p53 and anti-apoptotic protein bcl-2 may be prognostic factors in laryngeal epithelial lesions. Staining was performed on 57 paraffin-embedded biopsies from patients with clinically detected precancerous stages of the larynx. Histopathologic examination revealed normal epithelium in six cases, mild dysplasia in 20 cases, moderate dysplasia in 18 cases, severe dysplasia in seven cases, CA in situ in four cases, papilloma in one case and CA invasivum in one case. The p53 count in mild and moderate dysplasia was 26.8 and 38.6%, respectively. This difference was statistically significant. There was significant correlation between PCNA and p53 scores. There was also a relationship between the scores of these markers and bcl-2 expression. In ten out of 45 cases of dysplastic lesions the invasive cancer developed in 4 years of follow-up. The correlation between PCNA score and malignant progression of the dysplastic lesions was on the statistical borderline. There was significant relationship between malignant transformation and age of the patients.