Evaluation Of Tumor Aggressiveness Research Articles

Reactive Stroma in Prostatic Carcinoma and Correlation with Tumor Grade and Tumor Stage

Abstract Introduction. Reactive stroma co-evolves with prostatic carcinoma. The aim of this study is to establish stromal changes in the prostatic cancer tissue and to quantify those changes. Methods. Samples from 70 patients treated with radical prostatectomy due to prostatic cancer were used for this analysis. Stromal changes in prostatic cancer tissue were analyzed using histochemical stain Trichrome Masson and immunohistochemical stains Vimentin and Desmin and those changes were compared to the stromal composition in the surrounding benign prostatic hyperplasia. These changes were quantified as following: for the histochemical stain Trichrome Masson we measured the intensity of the stain and for the immunohistochemical stains Vimentin and Desmin we used the “stromal index” that combines the frequency and intensity of the signal. We correlated the received data between each parameters and with tumor grade and tumor stage using the Spearman rank correlation test. Results. There was significant correlation between Trichrome Masson staining intensity and tumor grade (R=0,27 p=0,023) and tumor stage (R=0,24 p=0,049), between Vimentin expression and tumor grade (R=0,35 p=0,003) and tumor stage (R=0,28 p=0,019) and between Desmin expression and tumor grade (R=−0,25 p=0,035). Conclusion. Analyses of the stromal composition and the expression of stromal markers in prostatic carcinoma and their quantification could serve as an additional tool in evaluation of tumor aggressiveness and tumor extension.

The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas.

Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas.Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas.Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas.Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically relevant information. Two novel quantitative criteria based on the complexity and the diversity measures enabled the identification of low or high aggressive prostate carcinomas and should be verified in the future multicenter, randomized studies.

Abstract P5-10-01: Clinical relevance of TP53 mutations and genomic instability in node positive breast cancer

Abstract Background - Aim: Malignant tumors are currently understood as genetic mosaics. For breast cancer (BC) patient assessment, the challenge remains to use the increasingly available tumor genomic data along with standard clinicopathological parameters. Methods: Histologically reviewed, paraffin tumor tissue DNA samples (N=1771), from patients who had received anthracycline-based adjuvant chemotherapy in the frame of 3 randomized trials by HeCOG (HE10/00, pre-trastuzumab [T]; HE10/05 &amp; HE10/08, post-T era), were investigated with targeted massively parallel sequencing (tMPS) for variants in 58 genes previously implicated in BC (custom panel, Ion Torrent systems). Upon multiple stringent quality filters, pathogenic coding mutations (MUT) and allelic (im)balance (AI, for 5 or more imbalanced SNPs; AI-high: at least 3 AI loci per sample) were evaluable in 1388 cases (78.4%). IHC4 (HER2 ASCO 2013 guidelines, Ki67 20% cutoff) was used for BC subtyping (luminal A, luminal B, luminal HER2, HER2-enriched and TNBC). Results: In total, 1264 tumors carried 1 or more MUT and 788 were positive for AI. No two tumors had the same genetic profile. Top 5 MUT genes (&amp;gt;5% of all cases) were TP53, PIK3CA, CDH1, GATA3 and MLL3; top 5 genes with &amp;gt;50% frequency within the tumor (possible drivers) were TP53, PIK3CA, GATA3, MAP3K1 and PTEN. Top imbalanced (unstable) loci included 5p15.33 (TERT), 7p12 (EGFR), 17p13.1 (TP53), 17q21 (BRCA1), 10p15 (GATA3) and 10q23.3 (PTEN). TP53 MUT were more prominent in HER2-enriched and TNBC (p&amp;lt;0.0001) and were strongly associated with AI (p&amp;lt;0.0001). Tumor genomic characteristics were modelled with 3-year disease-free survival (DFS) as end-point for the evaluation of tumor aggressiveness; patients without infiltrated lymph nodes (LN) were not evaluated in this analysis. In all 3 cohorts, 1-3 positive LN were favourable and &amp;gt;3 LN were unfavourable prognosticators. Among patients with HER2-negative tumors (evaluable N=851), those with &amp;gt;3 positive LN and AI-low tumors fared similarly to patients with 1-3 LN; those with AI-high tumors fared significantly worse (log-rank, p&amp;lt;0.0001). DFS for AI-low TNBC was similar to luminal A and luminal B tumors, while AI-high TNBC fared significantly worse (p=0.0007). Again in HER2-negative patients, TP53 MUT were associated with worse DFS irrespectively of subtype (p&amp;lt;0.0001). Among patients with HER2-positive tumors (evaluable N=246), DFS for T-treated patients (N=100) without TP53 MUT was similar to those who did not receive T, while T-treated patients with TP53 MUT fared significantly better (p=0.011); AI-high was an adverse prognosticator only for patients with &amp;gt;3 positive LN who did not receive T, while this feature did not interfere with outcome in T-treated patients or in non-T-treated patients with 1-3 LN (p&amp;lt;0.0001). Conclusions: This prospective-retrospective translational research study, one of the largest presenting tMPS data from paraffin tissues, confirms the extensive genetic diversity of BC at the individual tumor level. Genomic (in)stability, as assessed with AI and TP53 MUT status, may help in further defining prognosis in BC patients with early aggressive disease. TP53 MUT are indirectly shown to predict for T-specific benefit, which merits validation in larger cohorts. Citation Format: Vassiliki Kotoula, Sotiris Lakis, Zoi Alexopoulou, Elpida Charalambous, Kyriaki Papadopoulou, Aggeliki Lyberopoulou, Eleftheria Tsolaki, Eleni Timotheadou, Dimitrios Pectasides, Flora Zagouri, George Pentheroudakis, Angelos Koutras, Helen Gogas, Konstantine T Kalogeras, Ralph M Wirtz, George Fountzilas. Clinical relevance of TP53 mutations and genomic instability in node positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-10-01.

Urinary Bladder Cancer: The Current and Potential Role of MR Imaging in Non-Distant Metastatic Lesions

Urinary bladder cancer is the second most common genitourinary malignancy in Westernized countries. A number of emerging imaging techniques have recently been reported in the literature for use in imaging bladder cancer. While the explicit application of MR imaging in bladder cancer especially in non-distant bladder cancer or bladder cancer localized in pelvic remains uncertain and awaits a thorough evaluation. Therefore, this article aims to make a systematic review of previous literature and provide a complete assessment of the value of MR as an evolving imaging tool in localized urinary bladder cancer application. Studies were conducted by searching the MEDLINE and PubMed databases up to 2012 using both medical subject heading (Mesh) and a free text method like “urinary bladder cancer”, “magnetic resonance imaging” or “MRI”, “diffusion weighted imaging” or “DWI”. About 53 articles were selected and analyzed which were considered to be associated with the objective of this systematic review (Table 1). Results showed that MRI especially the newer functional imaging technique like DWI may has a great potential role in localized bladder cancer like early detection, staging, evaluation of tumor aggressiveness and therapeutic responsiveness of patients in the assessment of urinary bladder cancer and so forth. Newer MRI has already proceeded promising results in bladder cancer application; and the explicit role of newer MRI in bladder cancer patients still needs further research and awaits to be thoroughly evaluated.

11C-acetate for positron emission tomography imaging of clinical stage IA lung adenocarcinoma: comparison with 18F-fluorodeoxyglucose for imaging and evaluation of tumor aggressiveness

To determine the usefulness of positron emission tomography (PET) with (11)C-acetate (AC) for imaging lung adenocarcinoma and evaluating its tumor aggressiveness, AC- and (18)F-fluorodeoxyglucose (FDG)-PET were compared. One hundred and sixty-nine adenocarcinomas with clinical stage IA and 53 benign nodules were examined by both AC- and FDG-PET before surgery. The sensitivity and specificity for discriminating benign/adenocarcinoma were compared between AC- and FDG-PET. The AC and FDG uptakes were examined to determine the relationship with tumor aggressiveness, i.e., pathological tumor stage, lymphatic, vascular, or pleural involvement, and proliferative activity determined by Ki-67 staining score. While the sensitivity of AC-PET was significantly higher than FDG-PET for bronchioloalveolar carcinoma (BAC) and well-differentiated (W/D) adenocarcinoma (p < 0.001 and 0.006, respectively), there was no significant difference for moderately or poorly differentiated adenocarcinoma. The specificity was not different between them. While FDG uptakes were significantly higher in tumors with pathological advanced stages or those with lymphatic, vascular and/or pleural involvements than in tumors with pathological stage IA or those without these tumor involvements (p = 0.04 to p < 0.001), AC uptake did not show significant differences between the respective sub-groups except according to the tumor stage. While both AC and FDG uptakes showed a significant correlation with Ki-67 staining scores (p = 0.03 and p < 0.001, respectively), the correlation coefficient of former was lower than that of latter (p = 0.07). While AC-PET can image BAC and W/D adenocarcinoma with a higher sensitivity than FDG-PET, it cannot evaluate tumor aggressiveness of clinical stage IA lung adenocarcinoma as well as FDG-PET.

Oncofetal fibronectins in oral carcinomas:

Different isoforms of fibronectin are derived from a single gene by alternative processing of the primary RNA transcript or by posttranslational modifications. We have previously demonstrated that an oncofetal fibronectin (FN) isoform derived by O-glycosylation is highly associated with malignancy in breast and oral tumors. Another oncofetal FN isoform containing the ED-B sequence is derived by alternative splicing, and FN containing ED-B has been found to be a stromal marker of malignancies in various tissues. Here we report a comparative study by immunohistology of the distribution of the ED-B-containing isoform and the oncofetal FN isoform derived by O-glycosylation, in oral squamous cell carcinomas, premalignant lesions, and normal oral mucosa. A selective expression of the ED-B-containing isoform was demonstrated in close relation to the invading carcinoma (38/38), whereas there was virtually no staining in submucosa underlying premalignant lesions (1/11) and normal epithelium (0/5). The ED-B-containing FN showed close co-distribution and staining pattern with the oncofetal isoform derived by O-glycosylation. These results demonstrate that accumulation of FN adjacent to oral carcinomas includes both the ED-B-containing isoform and the isoform derived by O-glycosylation. Although both the change in primary structure and glycosylation of FN create conformational and immunologically detectable changes, the functional consequences in association with invasive carcinoma are poorly understood at present. Diagnostic implications especially of borderline lesions as well as evaluation of tumor aggressiveness may, however, be important.

Evaluation of tumor aggressiveness in breast carcinoma according to a scoring method.

A scoring system was used to classify 310 patients with breast carcinoma. Tumors were divided and scored according to their architectural patterns and histological features of known prognostic significance such as tumor volume, nuclear grade, mitosis, etc. According to the scoring value, tumors were classified as aggressive (A), moderately aggressive (M), and low aggressive (L). Results showed a higher rate of metastasis in patients with A tumors (72%) and M tumors (63%) when compared with L tumors (22%). There were 175 patients with axillary lymph node metastasis. Of these, 101 had A tumors, 91 had recurrences (90%), and 81 died (80%); of the 56 patients with M tumors, 26 had recurrences (46%) and 9 died (16%) (P less than 0.001). None of the 18 cases classified as L recurred (P less than 0.001). There were 135 patients with no nodal metastasis: 39 had A tumors (21 recurrences [54%] and 19 deaths [49%] and 96 had M and L tumors (1 recurrence [1%] and no deaths) (P less than 0.001).