Conventional Grading System Research Articles

RhoA protein expression correlates positively with degree of malignancy in astrocytomas

Astrocytic tumors are the most common intracranial neoplasms. Their prognoses correlate with a conventional morphological grading system that suffers from diagnostic subjectivity and hence, inter-observer inconsistency. A molecular marker that provides an objective reference for classification and prognostication of astrocytic tumors would be useful in diagnostic pathology. RhoA, a GTPase protein involved in cell migration and adhesion, has been shown to be upregulated in a variety of human cancers. Based on direct analysis of clinical materials, our study demonstrates increased expression of RhoA in high-grade astrocytomas. This observation may be relevant to astrocytoma biology and the development of potential therapeutics against high-grade astrocytomas. Of more immediate consequence, utilization of this marker may aid in the routine pathological grading (and hence prognostication) of astrocytomas.

Molecular markers in bladder cancer

Bladder cancer is one of the malignancies for which extensive information regarding molecular pathogenesis and genetic predictors of natural history as well as response to various modalities of treatment based on molecular profile is available. As more prognostic markers are being investigated in clinical trial settings, in the not very distant future we will be able to use these predictive markers in clinical decision-making. Bladder cancer is the second most common genitourinary tumor and is a significant cause of morbidity and mortality. A need for tumor markers that can be incorporated into clinical practice to add prognostic information and to refine the conventional TNM and grading systems in terms of treatment response and prognosis is crucial. Intravesical and systemic chemotherapy in bladder cancer are limited in their efficacy in the treatment of bladder cancer patients primarily when they are unable to induce apoptosis in bladder tumor cells. Understanding the apoptotic signals and the cascade of reactions that give pro-survival signals will go a long way in refining the treatments and will help in the future to individualize cancer therapies. It is imperative to study the role of these mechanisms in prospective clinical trials in a quest to find predictive markers that can help to tailor treatments, keeping in view the molecular heterogeneity.

Telomerase reverse transcriptase subunit expression is associated with chondrosarcoma malignancy.

Expression of the telomerase reverse transcriptase subunit telomerase reverse transcriptase gene is associated with most human malignancies. Because telomerase reverse transcriptase is rarely expressed in normal tissue, its presence in pathologic specimens is considered a marker of transformed cells. Moreover, high levels of expression have been correlated with poor prognosis in many cancers. Although telomerase activity has been found in chondrosarcomas, its prognostic significance in these malignant cartilage tumors is unknown. Malignancy in cartilage-derived tumors is assessed routinely by histomorphologic grading, but even well differentiated, low-grade lesions can metastasize. This unpredictable behavior greatly complicates the clinical treatment of cartilage tumors, making better prognostic indicators desirable. To address this issue we used immunohistochemistry to compare telomerase reverse transcriptase expression in a collection of 61 tumors consisting of malignant chondrosarcomas of varying grade and benign enchondromas. Associated case histories were reviewed to test the hypothesis that telomerase reverse transcriptase expression levels correlated with subsequent tumor recurrence. We found that the relative abundance of telomerase reverse transcriptase-expressing cells correlated significantly with grade and recurrence. These findings indicate that telomerase reverse transcriptase immunostaining may be a useful adjunct to the conventional three-level grading system.

Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems

Aim: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. Methods: The...

Prognostic markers in muscle invasive bladder cancer.

Current tumor, node, and metastasis (TNM) staging and grading systems are insufficient to accurately predict the evolution of most invasive bladder cancers irrespective of treatment. Predicting which invasive tumors will or will not recur or metastasize early is crucial in order to dictate initial therapy and to better counsel the patient. A need for tumor markers that could be incorporated into clinical practice to add prognostic information to the conventional TNM and grading systems in terms of treatment response and prognosis is crucial. This review provides an update on the most promising reported single markers and pathways, including the cell cycle markers p53, p21 and p27, and potential targets for novel therapies, such as cyclooxygenase 2 (COX 2) and factors of angiogenesis. The critical steps remain the availability of large and well-characterized data sets to validate the combination of markers, as well as high throughput methods to study tumor molecular fingerprints, such as DNA microarrays.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder?

Objectives. To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. Methods. The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. Results. VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors ( P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors ( P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. Conclusions. Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Identification by quantitative chromatin pattern analysis of patients at risk for recurrence of superficial transitional bladder carcinoma.

Based on the actual clinical outcomes of 132 fully documented patients with superficial transitional cell carcinoma of the bladder, we characterize the risk of recurrence and/or progression by computer assisted image microscopy applied to Feulgen stained nuclei. Each tumor was characterized by the conventional grading and staging systems as well as by cytometry generated variables describing nuclear DNA content, nuclear morphometry and chromatin patterns. These data were submitted to discriminant analysis to establish a model distinguishing between 2 groups of patients. Group 1 included cases with remission for more than 60 months and group 2 cases presented with recurrence with or without progression within 12 months of transurethral bladder resection. This latter model was then validated by Kaplan-Meyer analysis of the full data set. As evidenced by Kaplan-Meier analysis, the discriminant factor generated by discriminant analysis of cytometry generated variables provided a cutoff value for distinguishing between low and high risks of recurrence (p <0.00001). In contrast, conventional grading and staging systems were not able to make such efficient distinction. These 2 groups can be used as references with which new cases can be compared to prognosticate disease behavior independently of histopathological grading and/or clinical staging.

IDENTIFICATION BY QUANTITATIVE CHROMATIN PATTERN ANALYSIS OF PATIENTS AT RISK FOR RECURRENCE OF SUPERFICIAL TRANSITIONAL BLADDER CARCINOMA

Purpose: Based on the actual clinical outcomes of 132 fully documented patients with superficial transitional cell carcinoma of the bladder, we characterize the risk of recurrence and/or progression by computer assisted image microscopy applied to Feulgen stained nuclei.Materials and Methods: Each tumor was characterized by the conventional grading and staging systems as well as by cytometry generated variables describing nuclear DNA content, nuclear morphometry and chromatin patterns. These data were submitted to discriminant analysis to establish a model distinguishing between 2 groups of patients. Group 1 included cases with remission for more than 60 months and group 2 cases presented with recurrence with or without progression within 12 months of transurethral bladder resection. This latter model was then validated by Kaplan-Meyer analysis of the full data set.Results: As evidenced by Kaplan-Meier analysis, the discriminant factor generated by discriminant analysis of cytometry generated variables pr...

Evaluation of Ki67 antigen using MIB1 antibody as a prognostic factor in renal pelvic and ureteral cancer

(PURPOSE). Recently, several reports showed that immunohistochemistry using MIB-1 antibody, which recognizes Ki-67 antigen, is one of the useful methods to determine the proliferative activity in various cancer. To evaluate the prognostic usefulness of the MIB-1, antibody we assessed the cell proliferation immunohistochemically in urothelial cancer. (METHODS). The proliferative activity of thirty cases of renal pelvic and ureteral cancer has been investigated immunohistochemically using MIB-1 antibody, which recognizes Ki-67 antigen, a human nuclear antigen expressed in proliferating cells. (RESULTS). The Ki-67 index correlated with prognostic factors such as pathological stage and histological grade. The patients with early stage or low grade tumors had lower Ki-67 indices. And the Ki-67 index significantly correlated with recurrence and prognosis. The tumors of patients with recurrence or cancer death had higher Ki-67 indices. When the patients were suggrouped according to Ki-67 indices (more than 22%) had significantly worse prognosis even in the same grade. Especially in the grade 2 group, all the four patients in the higher Ki-67 index subgroup had recurred and died of cancer, whereas, in the subgrouped patients with tumors of lower Ki-67 indices, only three patients had bladder cancer recurrence, and no patients had died of cancer, except one case with advanced tumor (T4, N3, M0) resected incompletely. (CONCLUSIONS). These results indicate that the Ki-67 index is a useful prognostic factor and may enhance the prognostic accuracy determined by conventional morphological grading systems.

Neuro‐endocrine Cells—A New Prognostic Parameter in Prostate Cancer

Neuro-endocrine cells are a recognised component of prostatic ducts and acini. Half of all clinically manifest cancers show neuro-endocrine differentiation. Occult carcinomas have a lower incidence of such differentiation. Neuro-endocrine cells are of major prognostic importance and appear more reliable in predicting patients' survival than do conventional histological grading systems.

Granzyme A and perforin as markers for rejection in cardiac transplantation

The use of granzyme A and perforin as markers for rejection after cardiac transplantation has been investigated. Using in situ hybridization we have detected lymphocytes expressing granzyme A and perforin RNA that are infiltrating the donor heart after transplantation. A total of 29 different biopsies from 17 different patients who had undergone cardiac transplantation were examined. Twelve biopsies classified by conventional histological criteria as showing evidence of rejection were found to contain lymphocytes expressing granzyme A and perforin. Seven biopsies classified as showing no histological evidence of rejection infiltrating lymphocytes were found not to be expressing granzyme A or perforin. However, in 10 other biopsies from 5 different patients that had been classified as showing no evidence of rejection by the conventional grading system, lymphocytes expressing granzyme A and perforin were detected. In six of these cases the patient was found to have undergone a subsequent rejection episode. In the other four cases the biopsies were either taken at a very early stage after transplantation and the high doses of immunosuppression used routinely at that stage are likely to have averted any rejection episodes, or it was not possible to follow subsequent rejection episodes. These results, which are statistically significant (p = 0.06), demonstrate that granzyme A- and perforin-expressing lymphocytes can be identified in rejecting biopsies before histological damage is seen. The identification of perforin and granzyme A expression in vivo suggest a possible role for these proteins in the cytolysis that occurs during transplantation rejection. Furthermore, the data presented here suggest that it may be possible to use granzyme A and perforin as early predictive markers of transplantation rejection.

Systemic mastocytosis in 16 dogs.

The clinical and pathologic features of systemic mastocytosis in 16 dogs are reported. There was no apparent breed or sex predilection, and the median age at presentation was 9.5 years. In 14 of 16 cases there was a primary cutaneous mast cell tumor (MCT). When cutaneous tumor location was compared with previous reports, there was no association between location and systemic dissemination. The most common presenting signs associated with the cutaneous tumor were regional dissemination, edema, ulceration, and abscessation. They were present in 12 dogs (69%). Signs of systemic illness, including anorexia, vomiting, and diarrhea, were seen in eight dogs (50%). Other than the cutaneous tumors, the most consistent physical and radiographic abnormalities included lymphadenopathy, splenomegaly, and hepatomegaly. Eosinophilia and basophilia were seen in two and five dogs, respectively. Six dogs had increased numbers of mast cells in peripheral blood or buffy coat smears. Five of the nine dogs evaluated had increased numbers of mast cells in bone marrow aspirates. Bone marrow aspiration was superior to both peripheral blood and buffy coat smears in predicting mastocytosis. Coagulation abnormalities were seen in three of five dogs tested. Using a conventional histomorphologic grading system, 10 of 13 (77%) tumors were classified as Grade III or undifferentiated and were overrepresented when compared with previous reports of cutaneous MCTs. Eighty-eight percent of the dogs either died or were euthanatized because of their tumors. Organs commonly involved at necropsy included lymph nodes, spleen, liver, and bone marrow; four dogs had gastroduodenal ulcers.

Reliability of Palpation of Pedal Pulses As Ascertained by the Kappa Statistic

An improved statistic (weighted Kappa) was tested for reviewing the reliability of the palpation of pedal pulses by three observers. Significant improvement was noted after training. Reliability also persisted with respect to a reduced form of the conventional ordinal grading system. The findings indicated that problems of usefulness or reliability may arise when more than five distinctions are made in describing the pulses or when the data are completely reduced to only a dichotomous (present-absent) system.

Viewpoint: External Degrees: Myths and Realities

Viewpoint: External Degrees: Myths and Realities

Ultrastructure of mucoepidermoid carcinoma in minor salivary glands

Three cases of mucoepidermoid carcinoma of minor salivary glands were studied by electron microscopy. Mucus-secreting cells contained numerous mucous globules and bundles of fine cytoplasmic filaments. Another cell type contained a large number of glycogen particles, akin to tumor cells in glycogen-rich adenocarcinoma, and it is postulated that these cells represent the intermediate cells observed by light microscopy. Epidermoid cells contained a moderate amount of tonofilaments and various numbers of organelles. Mucus-secreting and epidermoid cells that surrounded a cystic space exhibited many microvilli. Results of this study support the theory that mucoepidermoid carcinoma develops from salivary gland duct cells with different cellular differentiation potentials and, in general, agree with the conventional grading system of mucoepidermoid carcinoma.

An analysis of the pass‐fail grading system as compared to the conventional grading system in high school chemistry

An analysis of the pass‐fail grading system as compared to the conventional grading system in high school chemistry