Mean nuclear area of fine needle aspirates of primary preoperative palpable breast carcinoma using image cytometry

OBJECTIVE: Early, operable breast cancers in appropriate patients are increasingly being treated preoperatively using neoadjuvant chemotherapy. A good response rate is seen with high grade tumors. Nuclear size, which may reflect the grade of the tumor, is also of possible prognostic value in breast cancer. STUDY DESIGN: We measured the mean nuclear area (MNA) of 114 consecutive preoperative fine needle aspirates of palpable, operable breast cancers. We used computerized image cytometry to measure nuclear area to determine tumor biology and possible grade prior to treatment. RESULTS: Histologic grade distribution was as follows: low grade, 15%; moderate grade, 40%; and high grade, 45%. Mann-Whitney test for trend on tumor size and histologic grade between MNA showed a significant relationship between MNA and tumor size (P=.016) but no significance between MNA and histologic grade (P =.22). The chi2 and Fisher Exact Test between MNA and node-positive or -negative patients showed no significance. CONCLUSION: When correlating MNA with tumor size and histologic grade, high MNA is present at a higher frequency as tumor size and histologic grade increase.     

Prognostic value of morphometry in low grade papillary urothelial bladder neoplasms

OBJECTIVE: To analyze the prognostic value of morphometry in low grade papillary urothelial bladder neoplasms (LGPUBNs). STUDY DESIGN: The primary (most common) and secondary (second most common) histologic grades were considered in accordance with the 1998 World Health Organization/International Society of Urological Pathology and the 1999 World Health Organization classifications. With the primary grade, 54 cases were papillary urothelial neoplasms of low malignant potential (PUNLMPs) and 66 low grade papillary urothelial carcinomas (LGPUCs), whereas the secondary grade consisted of 45 PUNLMPs and 75 LGPUCs. To assess the proliferative index, an immunohistochemical study was performed. Regarding nuclear morphometry, an image analysis system on Feulgen-stained sections was utilized in different tumor zones (Zs): Z 1, 100-150 cells from the outer layers of the papillae; Z 2, 100-150 cells from the inner layers; and Z 3, 10 largest nuclei. In univariate studies, a t test, and Mann-Whitney U test and Kaplan-Meier curves were applied, whereas a Cox regression model was used for multivariate study of the variables: size, multiplicity, maximum Ki-67 index, mean nuclear area (MNA) and SD, mean nuclear perimeter and SD, and roundness factor. RESULTS: All 120 cases were followed for a mean of 76.6 months (range, 36-168). In univariate studies, many variables showed a significant correlation (p < 0.05) with recurrence prediction, relapse-free interval and histologic grade regardless of adjuvant therapy. Otherwise, only the MNA of the 10 largest nuclei (threshold, 52 microm2) and the maximum proliferative index (threshold, 7.9%) appeared as independent prognostic markers in the multivariate study. CONCLUSION: In LGPUBNs, the independent prognostic value of MNA of the 10 largest nuclei as well as the maximum proliferative index indicates the importance of histologic grade assessment based on the secondary (second most common) grade.     

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.     

Prognostic significance of mean nuclear volume in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the correlation of stereologically estimated mean nuclear volume of tumor cells with other clinicopathologic prognostic features and survival in pancreatic ductal adenocarcinoma. STUDY DESIGN: The study included 27 patients with primary pancreatic ductal adenocarcinoma. A stereologic method proposed by Gundersen et al was used for the estimation of mean nuclear volume in hematoxylin and eosin-stained histologic sections of each case. Mean nuclear volume values were compared statistically with histopathologic prognostic feature groups and survival. RESULTS: The mean nuclear volume values of tumor cells ranged from 296.83 to 982.79 microns 3 (mean, 633.906 +/- 212.310). Higher values of mean nuclear volume were significantly related to advanced tumor stage and the presence of distant metastasis (Kruskal-Wallis, P = .036; Mann-Whitney U, P = .020). In contrast, nodal stage, tumor grade, perineural invasion, lymphatic and blood vessel invasion, and size of tumor showed no statistical relation to mean nuclear volume of tumor cells. Mean nuclear volume was found to be a significant predictor of survival in univariate analysis (P = .016). CONCLUSION: Estimation of mean nuclear volume may help in predicting the extent of disease and clinical behavior in pancreatic adenocarcinoma.     

Prognostic value of pS2 protein and receptors for epidermal growth factor (EGF-R), Insulin-like growth factor-1 (IGF-1-R) and somatostatin (SS-R) in patients with breast and ovarian cancer

The prognostic value of EGF-R, IGF-1-R and SS-R, and of cytosolic estrogen-regulated pS2 protein, was studied in patients (pts) with primary breast and advanced ovarian cancer. Ovarian cancer tissues were negative for pS2 (by immunoradiometric assay) IGF-1-R and EGF-R contents (by ligand binding assay, LBA) were of no or moderate prognostic value for breast cancer pts (n = 214). For advanced ovarian cancer pts, EGF-R content determined by LBA (n = 55) showed no prognostic value, whereas EGF-R status (n = 55) determined by immunohistochemistry (MoAb 2E9) signiificantly correlated with progression of disease (P < 0.05). In breast cancer pts, both SS-R and pS2 showed no association with tumor size, nodal status and grade. For pS2 the best cut-off level with respect to relapse-free (RFS) and overall survival (OS) was found to be 11 ng/mg protein. Both SS-R (1 g% SS-R+, n = 135; P < 0.04) and pS2 (27% pS2+, n = 197; P < 0.001), which were mainly positive in ER+ tumors, were of prognostic value, especially within the subgroups with ER+/PgR+ tumors. Also within N+ and No pts the 5-yr RFS and OS showed a difference between pS2+ and pS2- (33 and 54% for N+, and 31 and 13% difference for No pts). In summary, SS-R and pS2 are valuable pronosticators in breast cancer pts, and prognostic significance of EGF-R in ovarian cancer pts needs further study.     

Nutritional status, dietary intake and oral quality of life in elderly complete denture wearers

doi: 10.1111/j.1741‐2358.2011.00545.x Nutritional status, dietary intake and oral quality of life in elderly complete denture wearers Background and objective: The prevalence of malnutrition increases with age because of many factors. Edentulousness leads to the avoidance of many types of foods. The aim of this study was to determine whether elderly complete denture wearers have a higher risk of malnutrition than dentate controls. Material and methods: A Mini‐Nutritional Assessment (MNA) and a 3‐day dietary record were compiled for a group of fully dentates (21 women and 29 men; mean age 70.1 ± 6.1) and for a group of complete denture wearers (31 women and 16 men; mean age 70.1 ± 8.1). Socio‐demographic data and scores on the General Oral Health Assessment Index (GOHAI) questionnaire were collected. Results: Inter‐group comparison of MNA scores showed that more subjects in the edentulous group (21.3%) risked malnutrition than in the dentate group (0%). The variability of the MNA could be explained for 22% by dental status, 7% by loneliness and 4% by the GOHAI score (regression analysis). Both groups had insufficient energy intakes and deficits in vitamins and micronutrients; moreover, edentulous subjects had lower intakes than dentate subjects. Conclusion: The use of conventional dentures increases the risk of malnutrition in the elderly.     

Prognostic Factors of Primary Intraosseous Squamous Cell Carcinoma (PIOSCC): A Retrospective Review

ObjectivesTo delineate clinical and pathological features and determine the prognostic factors of primary intraosseous squamous cell carcinoma (PIOSCC).ResultsA total of 77 patients with PIOSCC were included in the study. Mean age at diagnosis was 58.8 years, (range, 37−81 years). Of the 77 patients, there were 58 men and 19 women. The most common location of disease was the mandible (71.42%), particularly the posterior mandible. The common presenting symptoms included jaw swelling (79.2%) and ulceration (42.65%). The estimated 2-year and 5-year overall survival were 68.9% and 38.8%, respectively. Univariate analysis identified the following as negative prognostic factors: histological grade, N classification, nodal status and treatment modalities. However, multivariate analysis determined positive nodal status, high histological grade and advanced N classification as the independent significant prognostic factors.ConclusionOur results demonstrate several clinical and pathological features of PIOSCC and identify important prognostic factors associated with overall survival in PIOSCC. These prognostic factors include nodal status, histological grade, N classification, and treatment modalities, all of which are important for patient counseling and may be useful for the development of new treatment approaches.     

Cell Cycle Regulation Targets of MYCN Identified by Gene Expression Microarrays

Background: We have previously shown that MYCN knockdown causes a G1 arrest in MYCN amplified (MNA), p53 wild type (wt) and p53 mutant MNA neuroblastoma cell lines, with increases in p21WAF1 and hypo RB in p53 wt cell lines. 1 Hypothesis: MYCN acts by inhibiting p21WAF1, and also by p21 independent mechanisms to override the G1 checkpoint in exponentially growing cells. Methods: Genes potentially regulated by MYCN were identified using gene expression microarrays in p53 wt MNA IMR-32 and p53 mutant MNA SKNBE(2c) neuroblastoma cell lines treated with MYCN or scrambled siRNA. Results were validated using qRT-PCR and confirmed using the regulatable MYCN expression system (SHEP Tet21N). Results: MYCN knockdown altered the expression of several cell cycle related genes. SKP2 was down regulated in both cell lines, and up regulated in MYCN+ Tet21N cells. Expression of the WNT antagonist DKK3 increased in both cell lines and decreased in MYCN+ Tet21N cells. Expression of CDKN1C (p57cip2) and TP53INP1 also increased after MYCN knockdown. Conclusions: MYCN may override the G1 checkpoint through down-regulation of SKP2 and TP53INP1 resulting in reduced p21WAF1 expression in p53 wt cell lines, and in addition may act through the WNT signalling pathway in a p53 independent manner.     

Prognostic value of plasminogen activator inhibitors in breast cancer

The prognosis of cancer is primarily dependent on its potential to invade and metastasize. Data from both preclinical and clinical studies strongly suggest that serine proteases, as well as their inhibitors and receptor, play a central role in the processes leading to metastasis. We therefore investigated the prognostic value of plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2) and the combination of both inhibitors in 332 patients with operable breast cancer. PAI-1 and PAI-2 content was measured in the primary tumor cytosols using an enzyme-linked immunosorbent assay. For PAI-1 the median value (3.9 ng/mg protein) was used as cutoff, while the optimized cutoff for PAI-2 (6.5 ng/mg protein) was obtained using the log-rank statistic. After a median follow-up of 46 months 96 (29%) patients relapsed. In univariate analysis patients with a high PAI-1 or a low PAI-2 content had an increased risk of relapse. The difference was statistically significant for PAI-1 (p<0.0001) and almost statistically significant for PAI-2 (p=0.057). Stage, tumor size, differentiation grade, lymph node status and hormone receptor status also showed significant univariate impact on disease-free survival (DFS). In multivariate analysis (Cox model) PAI-1 (p<0.0001, RR=2.78), PAI-2 (p=0.0075, RR=2.17), UICC stage (p=0.0014, RR=2.2), differentiation grade (p=0.0097, RR=1.91) and nodal status (p<0.0001, RR=2.9) retained their significance. When both inhibitors were combined the worst prognosis was observed in patients with simultaneous high PAI-1 and low PAI-2 levels, whereas low PAI-1 in combination with high PAI-2 values indicated a very favorable prognosis. In conclusion, our study showed that both PAI-1 and PAI-2 had independent prognostic value in breast cancer. Combination of both inhibitors further improved the differentiation of patients with respect to prognosis.     

Measurement of primary tumor volume by PET–CT to evaluate risk of mediastinal nodal involvement in NSCLC patients with clinically negative N2 lymph nodes

Aim

The study aimed to determine a prognostic value of primary tumor volume measured on the basis of integrated positron emission tomography–computerized tomography (PET–CT) in terms of mediastinal nodal metastases (N2) prediction in non-small-cell lung cancer (NSCLC) patients with PET–CT N2 negative lymph nodes.

Methods

The records of 70 potentially operable NSCLC patients treated with surgical resection were analyzed. All patients underwent diagnostic, preoperative PET–CT, which was the basis for tumor volume calculations as well as the evaluation of N2 nodes status. The logistic regression analysis was employed to determine correlation between mediastinal nodal involvement and volume of primary tumor (izoSUV2.5 volume), that is the volume of primary tumor inside SUV 2.5 line, tumor histology, location (peripheral vs. central), hilar node status.

Results

A statistically significant correlation between mediastinal node involvement and izoSUV2.5 volume, tumor histology, locations peripheral vs. central and hilar node status was found. The risk of mediastinal lymph node metastasis is 24% for tumor volume of 100 cm³ and increases up to 40% for tumor volume of 360 cm³. An increase of tumor volume by 1 cm³ increases the risk of lymph node disease by 0.3%. Tumor histology adenocarcinoma vs. squamous cell carcinoma increases the risk of mediastinal lymph node involvement by 195%, location central vs. peripheral by 68% and hilar node involvement by 166%.

Conclusions

The study demonstrates that izoSUV2.5 volume of primary tumor may be considered as a prognostic factor in NSCLC patients, since it strongly correlates with mediastinal lymph node pathological status. This correlation is modified by primary tumor location, histology and hilar node involvement.     

The Role of Fibroblasts in Pancreatic Cancer: Extracellular Matrix Versus Paracrine Factors

BACKGROUND AND AIM: Desmoplasia is a characteristic feature and a suspected mechanism of tumor progression in pancreatic ductal adenocarcinoma (PDAC). Main constituents of the stroma involve cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM). The aim of this study was to dissect the interaction of CAFs, ECM, and PDAC cells in both an in vitro setting and a large-scale clinical cohort study. METHODS AND MATERIAL: Patients operated for PDAC were identified from our prospectively maintained clinical database. A standard pathology protocol was applied for pancreatoduodenectomy specimens also assessing CAF activation as either CAF grade 0 or CAF grade +. Interaction between a spectrum of pancreatic cancer cell lines (PCCs) and mouse embryonic fibroblasts (NIH 3T3) was assessed in a conditioned medium experimental setup. RESULTS: One hundred eleven patients operated for PDAC from 2001 to 2011 were identified. Univariate analysis disclosed CAF grade + (P = .030), positive M status (P < .001), and lymph node ratio (LNR) > 0.1 (P = .045) to impair overall survival. Independent prognostic factors were CAF grade (P = .050) and positive M status (P = .002). CAF grade correlated with N status (CC = 0.206, P = .030), LNR (CC = 0.187, P = .049), tumor size (CC = ?0.275, P = .003), and M status (CC = 0.190, P = .045). In the in vitro setting, paracrine effects of pancreatic cancer cell resulted in morphological activation of fibroblasts and tumor cell differentiation–dependent increase of fibroblast growth. Paracrine effects of poorly differentiated PCCs led to an upregulation of Vimentin in NIH 3T3 fibroblasts. Paracrine effects of fibroblasts on their part promoted cancer cell motility in all PCCs. As the second stromal component, fibroblast-derived ECM resulted in significantly decreased proliferation depending on density and led to upregulation of ZEB1 in poorly differentiated PCCs. CONCLUSION: In PDAC patients, positive CAF grading was identified as a negative prognostic parameter correlating with positive N status, high LNR, positive M status, and smaller tumor size. Whereas bilateral interaction of PCCs and CAFs promotes tumor progression, ECM poses PCC growth restrictions. In summary, our study discloses differential effects of stromal components and may help to interpret heterogeneous results of former studies.     

Flow cytometric study of DNA distribution in cytopunctures of benign and malignant breast lesions

One hundred seventy-eight cytopunctures of mammary lesions were obtained for cytologic diagnosis and flow cytometric (FCM) analysis of the nuclear DNA content. All lesions were excised and evaluated histologically; 106 were carcinomas and 72 were benign lesions. The benign lesions showed a diploid DNA content, with one exception. Among the 106 carcinomas, 35 (33%) were diploid, 14 (13%) were tetraploid and 57 (54%) were aneuploid. For 79 carcinomas, the relationship between ploidy and (1) "T" and "N" of TNM staging, (2) the histologic grading of Scarff, Bloom and Richardson, (3) axillary nodal involvement, (4) the presence of estrogen and progesterone receptors, (5) age and (6) menopausal status was investigated. The percentage of aneuploidy was significantly higher (P less than .05) in grade III tumors as compared to grade I tumors. There was no significant relationship between aneuploidy and the other factors. However, a trend was observed between the lack of steroid receptors and a high probability of the tumor being aneuploid. FCM DNA analysis was also carried out on breast carcinomas obtained at surgery in 40 patients for whom FCM DNA analysis had previously been performed on breast cytopuncture specimens. The FCM DNA analyses were found to be best performed on the samples obtained by cytopuncture, which may increase the yield of tumor cells.     

Prognostic value of S-phase fraction in 920 breast cancer patients: focus on T1N0 status

The aim of this study was to reexamine the prognostic role of tumor cell kinetics measured by S-phase fraction (SPF) and to establish its clinically relevant threshold values. SPF was determined by flow cytometry in a group of 920 consecutive breast cancer patients, all followed at our institute for 10 years (1988 to 1998). Mean age was 60.5 years (27-89 years). Median follow-up was 63 months (3-150 months). All patients had initial surgical treatment. SPF quartiles were: Q1=3.08%, median value = 5.98%, Q3=10.22%. A significant difference in overall specific survival was obtained between two populations divided by a cutoff at Q1 (p < 0.0001). A multifactorial analysis including SPF and known prognostic factors such as tumor size, node status, histological grade, ER and PR status was performed using the Cox model in a population of 719 patients: univariate analysis showed that each of these factors had significant influence on overall survival. Multivariate analysis selected three of them, ranked by decreasing order of hazard ratio (HR) value: SPF (HR: 3.88, p < 0.001), tumor size (HR: 2.49, p < 0.001) and nodal status (HR: 2.28, p < 0.001). In addition, when tumors were stratified according to SPF quartile values, there were statistically different overall survival curves in patients with small tumors (< 2 cm) and in axillary node-negative patients.     

Loss of cell cohesion in breast cytology as a characteristic of neuroendocrine carcinoma

OBJECTIVE: To characterize a specific group of breast cancers displaying a scattered single cell pattern in cytology and correlate it with histologic and immunohistochemical findings. STUDY DESIGN: Of 135 consecutive malignant breast cytologic specimens, 12 cases were selected for their scattered single cell pattern on aspiration cytology. Immunohistochemical staining for neuroendocrine markers and prognostic parameters was performed on paraffin sections of corresponding primary breast carcinomas. RESULTS: In the smears of the 12 cases, highly cellular neoplastic cells with a single cell pattern were observed predominantly. The tumor cells had relatively wide, granular cytoplasm and a low to moderate nuclear/cytoplasmic ratio. Histologically, they were arranged mainly in relatively large, solid nests and occasionally contained a tubular pattern with small amounts of stromal tissue. Five of the 12 cases demonstrated neuroendocrine differentiation with a positive immunoreaction for chromogranin A and synaptophysin. Except for the small mean size of the tumors (P < .01), no significant differences were identified among the prognostic parameters, including a nodal status, estrogen receptor status, growth fraction by Ki-67 or immunoreactivity for c-erbB-2, as compared with the other 123 cases. CONCLUSION: Loss of cell cohesion in breast cytology is a good morphologic marker for identifying neuroendocrine breast carcinoma.     

The expression of hTR and hTERT in human breast cancer: correlation with clinico-pathological parameters

Background

Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age.

Methods

Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression.

Results

The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples.No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen.

Conclusion

The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies.

     

Stereologic estimates of volume-weighted mean nuclear volume in aspiration smears of ductal breast carcinoma. Correlation with cytologic grade, tumor size and lymph node status

OBJECTIVE: To estimate cytologic volume-weighted mean nuclear volume and correlate it with other prognostic factors, such as tumor diameter and cytologic grading in relation to nodal infiltration. STUDY DESIGN: The relationships between nodal status and nuclear VV, tumor diameter and cytologic grading, according to the modified Black nuclear grading system, were analyzed on fine needle aspirates of 49 cases of breast cancer by univariate and multivariate logistic regression. RESULTS: Volume-weighted mean nuclear volume (nuclear VV) estimated on fine needle aspiration smears showed a significant correlation with grade of tumor differentiation. CONCLUSION: Stereologic evaluation of nuclear size by nuclear VV is an objective method for the cytologic grading of ductal carcinoma of the breast and has independent prognostic value in relation to nodal status higher than those of tumor diameter and cytologic grade.     

One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score

Purpose

The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score.

Methods

The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients.

Results

At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm³ (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698.

Conclusion

Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy.     

Karyometric features of low and high grade glial tumors as compared with their MRI appearance

OBJECTIVE: To compare the results of a magnetic resonance imaging (MRI) grading designed to identify low and high grade gliomas with karyometry used as a tool to grade primary brain tumors. STUDY DESIGN: A consecutive series of 23 primary brain tumors was selected for this study. The neuroradiologist, not knowing the histologic diagnoses, divided the cases into low and high grade categories on the basis of the following 7 features: border sharpness, heterogeneity without contrast, cavitation, contrast enhancement, hypervascularity, mass effect and perifocal T2 hyperintensity. To each feature was given a numerical value, ranging from 1 to 3. All the cases were reviewed and classified by the same pathologist, blinded to the MRI diagnosis. Two hundred nuclei per case were recorded, and 93 karyometric features related to nuclear area, total optical density and chromatin distribution were analyzed for each nucleus. Statistical analysis included discriminant analysis, Kruskal-Wallis test, nonsupervised learning algorithm P-index and Beale statistic. RESULTS: Ten cases were classified as low grade on the basis of their MRI features. The corresponding histopathologic diagnoses were: grade 2 astrocytoma in 2 cases and grade 2 oligodendroglioma in 8 cases. An MRI diagnosis of high grade tumor was made in 13 cases. In 10 cases it was confirmed by the histopathologic diagnosis (3 grade 3 astrocytomas, 1 grade 3 oligodendroglioma and 6 glioblastomas). In the remaining 3 cases the histologic examination revealed a low grade tumor, 1 grade 2 astrocytoma and 2 grade 2 oligodendrogliomas. For the purposes of the karyometric analysis the cases were allocated to the low or high grade category according to their histologic diagnosis (13 cases low grade and 10 cases high grade). Nuclei from low and high grade tumors showed clearly different karyometric characteristics. The oligodendroglioma nuclei had abnormality values close to the low grade standard, while the astrocytoma nuclei were a highly dispersed group with characteristics indicative of a higher degree of nuclear abnormality than the oligodendroglioma nuclei. The results of karyometric analysis showed that grade 2 tumors, corresponding to the low grade group, form a rather distinct category from grade 3 and 4 tumors belonging to the high grade group. CONCLUSION: The results of MRI grading based on a series of features that are routinely assessed by the neuroradiologist to reach a final diagnosis correlate highly with the histopathologic diagnosis. Karyometry can be a useful adjunct to histologic grading.