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High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in Node Metastasis in Primary Breast Cancers.

ABSTRACT: Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor receptor 2 (HER2) expression may vary during tumoral progression. We aimed to describe and compare ER, PR, and HER2 expressions in primary breast tumors and synchronic axillary nodal metastases, and evaluate phenotypic correlations between them.Patients were identified prospectively through surgical procedures between September 2013 and July 2016. The status of ER, PR, HER2, and Ki-67 were pathologically analyzed in breast cancers and axillary nodal metastases; these patients were classified based on the breast cancer phenotypes into five subgroups.Synchronic axillary nodal metastases were observed in 127 patients. In breast cancers and nodal metastases, correlation analyses of ER, PR, and Ki-67 expression showed a statistical dependence and concordance between these samples was unambiguously demonstrated through Bland-Altman plots for each determination. Primary breast tumors were classified as follows: luminal A, 41.6%; luminal B, 40.0%; luminal B/HER2, 9.6%; HER2, 2.4%; triple negative, 6.4%. Alterations in phenotype were observed in 28% of patients. The most frequent phenotypic alteration was from luminal B to A (36.4%). Ten cases (30.3%) showed alterations with therapeutic implications; six gained HER2 overexpression, and four, hormonal receptor (HR) expression. A moderate strength of agreement (Cohen's κ coefficient, 0.59; 95% confidence interval, 0.48-0.71) was observed. In multivariate analyses, high histologic grade (odds ratio [OR], 2.79; p<0.047) and high Ki-67 expression (OR, 1.05; p<0.037) were independent factors predictive of phenotypic alterations.Strong correlations were observed in HR and Ki-67 expressions between primary breast tumors and axillary nodal metastases, and a moderate concordance was observed in their phenotypical characteristics. Nevertheless, alterations did exist, and one-third of these changes may have therapeutic implications. The nodal metastases of tumors with high grade and high Ki-67 expression may need to be analyzed, to obtain complete therapeutic information.

SUBMITTER: Mando P

PROVIDER: S-EPMC5500400 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:BackgroundThis study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features.MethodsA total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA).ResultsHCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively).ConclusionsPreoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.

Project description:BackgroundThe objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure.ResultsThe first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86).ConclusionA definition of murine histologic alterations resembling asthma in the BALB/c OVA mouse was developed and validated. The definition will be of use in experiments involving this model to ensure that all mice said to have undergone an asthmatic attack did indeed reveal allergic pulmonary inflammation. Proposed grading criteria should be further evaluated with additional studies using physiologic measures of attack severity and increased airway resistance.

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High Histologic Grade and High Ki-67 Expression Predict Phenotypic Alterations in Node Metastasis in Primary Breast Cancers.

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