Immunohistochemical Grading Research Articles

Prognostic factors for first recurrence following meningioma surgery.

The present study investigated the role of the Simpson grade system, MIB-1 immunohistochemical marker, meningioma location and grade in the risk of recurrence. Between January, 2008 and January, 2018, the present study retrospectively evaluated all patients undergoing craniotomy for the resection of a histopathologically confirmed meningioma. Patients with neurofibromatosis, acoustic neurinomas and radiation treatment prior to surgery were excluded. After applying the exclusion criteria, 103 patients were included in the study. Following a mean follow-up period of 67.3±33 months, there were 12 cases (11.6%) of tumor recurrence. No significant association between meningioma recurrence and age, sex, or tumor location was found. When comparing the risk of recurrence between Simpson grades I, II, III and IV excisions, and between Simpson grade V, the difference was statistically significant. When comparing WHO grade I and II meningioma vs. grade III, the difference was significant. MIB-1 LI >3% exhibited a trend towards a significant association with the risk of recurrence. On the whole, the present study demonstrates that the Simpson grade is associated with the risk of recurrence. Patients with tumors with an MIB-1 index >3% may also be at a risk of recurrence. Notably, the present study proposed that in the case of recurrence, this is more likely to occur in an interval of 5.5 years following surgical intervention.

Relevance Analysis of TPM2 and Clinicopathological Characteristics in Breast Cancer.

The function of tropomyosin 2 (TPM2) in breast cancer is still far understudied. In this study, we aim to explore the roles of TPM2 in breast cancer progression. This research included 155 breast cancer tissues. The expression of TPM2 was analyzed by immunohistochemical staining and grading. The mRNA expression of TPM2 in pan-cancer was analyzed with The Cancer Genome Atlas (TCGA) data plate form. The differential expression of TPM2 protein and the differential promoter methylation level of TPM2 between breast cancer tissues and normal breast tissues were analyzed by the UALCAN online database. The relationship between TPM2 and signaling pathways was interpreted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway enrichment analyses. The survival curve of TPM2 was analyzed across the Kaplan-Meier plotter online database. Furthermore, the relationship between TPM2 expression and infiltrating macrophages was validated through in vitro co-culture experiments. TPM2 expression was significantly down-regulated in breast cancer samples. In addition, TPM2 expression was correlated with lymph node metastasis and high-grade histopathological morphology. The receiver operating characteristic (ROC) curve indicated that TPM2 expression could well distinguish between normal breast tissue and breast cancer tissue. TPM2 may have potential value in breast cancer diagnosis. Bioinformatics analysis illustrated that TPM2 was mainly involved in extracellular matrix organization, collagen fibril organization, cell junction assembly, focal adhesion, cAMP signaling pathway, estrogen signaling pathway, Wnt signaling pathway, and adaptive immune system. TPM2 expression was correlated with immune infiltrating cells and immune checkpoint molecules. Our in vitro co-culture experiments showed that the M2 macrophages could upregulate the expression of TPM2. TPM2 may play key roles in breast cancer occurrence and development, especially in cancer metastasis. TPM2 may be a potential biomarker for breast cancer diagnosis.

Correlation of Claudin18.2 expression with clinicopathological characteristics and prognosis in gastric cancer

ObjectivesClaudin18.2 (Cldn18.2) is a tight junction protein expressed in gastric epithelial cells and is an emerging target for gastric cancer (GC). This study aimed to analyze the correlation between Cldn18.2 and clinicopathological parameters in GC patients undergoing radical surgery. Methods and resultsThis study included 426 GC patients who underwent radical gastrectomy. The expression of Cldn18.2 was analyzed by immunohistochemical staining and grading. The statistical results indicated that the expression of Cldn18.2 was correlated with T stage, TNM stage, Lauren classification, and the expression level of Mucin-2 (MUC2), Mucin-5AC (MUC5AC), Mucin-6 (MUC6), human epidermal growth factor receptor 2 (HER2), P53 and trefoil factor 2 (TFF2). In addition, through data mining of the Cancer Genome Atlas (TCGA) database, it is suggested that Cldn18.2 expression level is significantly correlated with the expression level of MUC5AC, MUC6, and TFF2. Besides, Cldn18.2 is related to tumor immune infiltration, programmed cell death protein 1 (PD 1) pathway, cell cycle and Wnt signaling pathway. ConclusionsThe expression of Cldn18.2 was closely related to gastric-type GC, so gastric-type GC patients may benefit more from targeted drugs targeting Cldn18.2. In GC cells, depletion of Cldn18.2 may influence cell cycle and immune response by affecting Wnt signaling pathway and PD 1 pathway.

Assessing Oral Epithelial Dysplasia Risk for Transformation to Cancer: Comparison Between Histologic Grading Systems Versus S100A7 Immunohistochemical Signature-based Grading.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen's kappa ( K ) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement ( Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P =0.231; ( P >>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement ( Kw =0.892) and was a good indicator of transformation to cancer ( P =0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

Effect of the MiR-99b and MiR-135b on peritoneal carcinomatosis and liver metastasis in colorectal cancer

AimThis study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. Materials and methodsChanges in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. ResultsThe expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues (p < 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p < 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p = 0.045, p = 0.006, and p = 0.012, respectively). ConclusionWhile the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.

Correlation between expression of immunohistochemical markers and morphology in lung neuroendocrine neoplasms

lung neuroendocrine neoplasms embrace rather heterogeneous and rare malignancies which are usually characterized by nonspecific, “blurred” clinical signs thus complicating correct diagnosis or seriously delays it. Pulmonary neuroendocrine neoplasms accurate diagnostics and classification need to be improved. Histological examination should be supplemented by immunohistochemical tests to verify the neuroendocrine component, assess proliferative index of tumor cells, and confirm its bronchopulmonary origin. Immunohistochemistry is especially important in case of small or crushed biopsies, which account more than 50% of all specimens in lungs neuroendocrine neoplasms. Modern classification of lung neuroendocrine neoplasms and their grading are based on morphological criteria. Immunohistochemical markers expression is quite variable in different histological subtypes of bronchopulmonary neuroendocrine neoplasms, often data are descriptive, and correlation with morphology is studied insufficiently. The aim of this study was to define any significant correlation between different immunohistochemical markers expression, necrosis, proliferative index (Ki-67 ratio), and tumor grade in broncho-pulmonary neuroendocrine neoplasms. Histological blocks of lung neuroendocrine neoplasms from 113 unique patients (36 resections and 77 biopsies (54.5% of biopsies appeared to be small or crushed) were used in this study. The sample comprised 91 male and 22 female patients; the mean age was 59.2, CI 95% (56.9–61.4) years (from 19 to 77 years). Histological examination (including neuroendocrine morphology, necrosis, and grade) was provided in all cases. Also, immunohistochemistry, using Chr A, Syn, CD56, TTF-1, CK7, and Ki-67 before chemotherapy was performed. All morphological and immunohistochemical data were assessed by two different independent pathologists without the access to patient’s clinical data. All the observations were classified based on 2021 WHO Thoracic Tumors Classification. The sample was censored. We used nonparametric statistics (Spearman’s rank correlation) for this study. In was found that Chr A expression strongly (p&lt;0.05) correlated with immunohistochemical markers of primary lung malignancies (TTF-1 and CK7) that are mainly expressed in highly and moderately differentiated neuroendocrine neoplasms. Also, positive expression for TTF-1 and CK7 correlated with each other (p&lt;0.01). There was a strong negative correlation (p&lt;0.05) between Chr A staining and necrosis presence and it’s severity; between Chr A expression and tumor cells proliferation (Ki-67 ratio) (p&lt;0.01); and between Chr A labeling and tumor grade (p&lt;0.01). The correlation of immunohistochemical markers expression with necrosis, Ki-67 ratio and tumor grade was significant only for Chr A. All other tested options, for other markers were not statistically significant. It was defined that decrease or loss of Chr A expression reliably indicates tumors progression. Chr A expression can be used as an additional tool for grading of lung neuroendocrine neoplasms.

Does the Overall Survival of the Resectable Periampullary Carcinomas Correlate with High Expression of p53 and ki67?

Introduction: Periampullary carcinomas represent a group of tumors that develop in a complex area, implying different anatomical structures. The most common histological type of periampullary carcinomas is the adenocarcinoma. The pancreatic type of periampullary adenocarcinomas has the worst prognosis. Immunohistochemical markers, such as ki-67 and p53, can be used in predicting survival. Material and method: we selected the patients with periampullary adenocarcinomas, intestinal or biliopancreatic type, with resectable tumors, and we performed immunohistochemical stains for ki-67 and p53 markers. The overall survival was analyzed according to the expression of immunohistochemical markers, TNM staging, tumor grade and perineural invasion. Results: Sixty-seven patients were included in the study. The median overall survival for the whole cohort was 12 months, with a 2-year survival rate of 25%. High rate of tumor proliferation (ki67 more than 80%) was significantly associated with shorter overall survival (median survival 3 months compared with 17 months for the group with ki67 index less than 80%). A high expression of p53 protein has been associated with low overall survival. The low survival was associated with poorly differentiated tumor grade and lymph node status. Conclusion: Both immunohistochemical expression of ki67 and p53 can be used as prognostic and predictive factors for overall survival of patients with resectable periampullary adenocarcinomas.

Sclerostin Immunohistochemical Staining in Aggressive Maxillofacial Giant Cell Lesions: Initial Results and Potential Therapeutic Target.

Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs. This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests. A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient. Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

Expression of GATA3 and Cytokeratin 14 in Urinary Bladder Carcinoma (Histopathological and Immunohistochemical Study)

BACKGROUND: Urothelial carcinoma (UC) with squamous differentiation (SD) is the most common histologic variant of bladder carcinoma and its presence is associated with poor prognosis which may need early radical cystectomy to avoid progression and recurrence. It is difficult to detect few foci of SD, especially nonkeratinizing or early switch from urothelial to squamous epithelium on only morphological basis. Combination of GATA3 and Cytokeratin 14 (CK14) could be helpful in differentiating pure UC, UC with SD and pure squamous cell carcinoma (SCC). AIM: Assessment of GATA3 and CK14 expression in urinary bladder carcinoma and correlation with clinical and histopathological variables, for both diagnostic and prognostic purposes. MATERIALS AND METHODS: Sixty cases of archived paraffin blocks of urinary bladder carcinoma were tested for GATA3 and CK14 expression by immunohistochemistry using a rabbit monoclonal antibody against human CK 14 and mouse monoclonal antibody against GATA3, respectively. RESULTS: There is a significant correlation between GATA3 immunohistochemical expression and histological tumor subtypes of bladder carcinoma (p &lt; 0.001), i.e. the GATA3 is a useful marker for urothelial origin especially in papillary UC. There is a significant correlation between GATA3 immunohistochemical expression and UC grade (p &lt; 0.001). CK14 showed positive cytoplasmic staining in 9/14 (64.3%) cases of UC with SD and (13/13) (100%) cases of pure SCC and negative in 33/33(100%) cases of UC other than UC with SD. CK14 had sensitivity (64.3%) and specificity (100%) for areas of SD. CONCLUSION: GATA3 is a specific immunohistochemical marker for urothelial origin. CK14 is a highly specific and sensitive immunohistochemical marker of squamous cell carcinoma.

Lymphoma in Psittacine Birds: A Histological and Immunohistochemical Assessment.

In psittacine birds, round cell neoplasms that originate from lymphocytes, plasma cells, histiocytes, or mast cells are sporadic and poorly described. The lack of morphological and immunohistochemical diagnostic criteria or grading schemes make specific diagnoses and prognoses challenging. We assessed cases of psittacine birds diagnosed with round cell neoplasia from 3 North American veterinary diagnostic laboratories to describe the diagnostic features of these tumors. For all cases, demographic data, anatomic distribution, histological features, and immunoreactivity for T (CD3) and B (Pax5 and MUM-1) cell markers were assessed using tissue microarrays and whole slide mounts. Thirty-eight psittacine birds representing 14 species were included. Tumors were mainly infiltrative and multicentric, were composed of homogenous sheets of round to polygonal cells, and commonly presented with a high mitotic count (average 21 mitoses per high-power field). Based on Pax5 immunoreactivity, B-cell lymphoma was most common (19/38 [50%]), and was significantly associated with involvement of the gastrointestinal and urogenital systems. Of the 38 cases, 6 (16%) were consistent with T-cell lymphoma, 3 (8%) with plasma cell tumor, and 3 (8%) were double-reactive for both B- and T-lymphocyte markers. This is the first study to describe morphologic and immunohistochemical features of round cell neoplasia in a large number of psittacine birds, and provides benchmark data for future studies aimed at elucidating the diagnosis and prognosis of these neoplasms. These data also provide useful information about reactivity of commercially available antibodies as lymphocyte markers in tissues of multiple psittacine species.

Is there a connection between immunohistochemical markers and grading of lung cancer with apparent diffusion coefficient (ADC) and standardised uptake values (SUV) of hybrid 18F-FDG-PET/MRI?

To correlate tumour grading and prognostic immunohistochemical markers of lung cancer with simultaneously acquired standardised uptake values (SUV) and apparent diffusion coefficient (ADC) derived from hybrid PET/MRI. In this retrospective study, 55 consecutive patients (mean age 62.5±9.2years) with therapy-naïve, histologically proven lung cancer were included. All patients underwent whole-body PET/MRI using 18F-flourdeoxyglucose (18F-FDG) as a radiotracer. Diffusion-weighted imaging of the chest (DWI, b-values: 0, 500, 1000s/mm2 ) was performed simultaneously with PET acquisition. Histopathological tumour grading was available in 43/55 patients. In 15/55 patients, immunohistochemical markers, that is, phospho-AKT Ser473 (pAKTS473), phosphorylated extracellular signal-regulated kinase (pERK), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (erbB2) were available. The average SUVmax, SUVmean, ADCmin and ADCmean in lung cancer primaries were 12.6±5.9, 7.7±4.6, 569.9±96.1s/mm2 and 825.8±93.2s/mm2 , respectively. We found a significant inverse correlation between the ADCmin and SUVmax (r=-0.58, P<0.001) as well as between the ADCmin and SUVmean (r=-0.44, P<0.001). Tumour grading showed a significant positive correlation with SUVmax and SUVmean (R=0.34 and R=0.31, both P<0.05) and a significant inverse correlation with ADCmin and ADCmean (r=-0.30 and r=-0.40, both P<0.05). In addition, erbB2 showed a significant inverse correlation with SUVmax and SUVmean (r=-0.50 and r=-0.49, both P<0.05). The other immunohistochemical markers did not show any significant correlation. 18F-FDG-PET/MRI showed weak to moderate correlations between SUV, ADC, tumour grading and erbB2-expression of lung cancer. Hence, 18F-FDG-PET/MRI may, to some extent, offer complementary information to the histopathology of lung cancer, for the evaluation of tumour aggressiveness and treatment response.

The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. Results: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.

Immunohistochemical Grading of Epidural Fibrosis with CD105 Antibody

Grading of epidural fibrosis (EF) is usually performed by histopathologic staining in experimental studies. Immunohistochemical methods for grading are not available in routine practice yet. In our study, the effect of tranexamic acid (TXA), a commonly used hemostatic agent in surgical interventions, was evaluated for use against the development of EF with classical histopathologic methods and immunohistochemistry using the CD105 antibody, a marker of angiogenesis. Sixteen rats were used. The rats were assigned to 2 groups, control and TXA. Laminectomy was performed on the control group. In the treatment group, laminectomy+ topical TXA was applied. After sacrificing the rats in the sixth week, histopathologic and immunohistochemical examinations and grading of the EF tissue were performed. Conventional histopathologic parameters of fibroblast count, intensity of fibrosis density, and inflammatory cell density, as well as immunohistochemical evaluation with CD105, showed that the grading of EF was comparable between groups I and II (P < 0.001). The results of our study have demonstrated that CD105 is compatible with the conventional histopathologic grading methods and can be used as a marker to determine the grades of angiogenesis and fibrosis in experimental studies. The results of our study have also shown that TXA, administered locally for hemostasis, reduces the grade of EF in rats following laminectomy. TXA has been observed to cause no toxic effects on neural tissue as it is already commonly used in clinical practice.

Three-tiered score for Ki-67 and p16ink4a improves accuracy and reproducibility of grading CIN lesions

AimsTo investigate the accuracy and reproducibility of a scoring system for cervical intraepithelial neoplasia (CIN1–3) based on immunohistochemical (IHC) biomarkers Ki-67 and p16ink4a.Methods115 cervical tissue specimens were reviewed by three...

Abstract P2-03-09: An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank

Abstract Background: Subtyping of invasive breast cancer utilizing immunohistochemical stains for estrogen receptor, progesterone receptor, and HER2, with or without the proliferation marker Ki-67, is the current standard of care employed by pathologists. The development of the BluePrint® molecular subtyping assay by Agendia, a microarray-based gene expression test used in conjunction with MammaPrint, to molecularly subtype and assess recurrence risk in early-stage breast cancer, has breast surgeons and oncologists challenging the status quo. Study Objectives: With increasing emphasis placed of proper use of declining resources, the current study aimed to determine parameters in which such testing has the greatest added value. Materials and Methods: All invasive breast cancer biopsies and resection specimens with formalin fixed paraffin embedded tissue sent for testing at Agendia Genomics Laboratory from April 2015 to May 2017 were reviewed in an institutional look back. 87 cases were reviewed and conventional immunohistochemical cancer profiling, tumor size, and grade were compared with MammaPrint prognostic reports. Results and Discussion: Of the 87 cases compared, 67 (77%) showed concordance between immunohistochemical and molecular subtyping. Of the 20 discordant cases, 13 (65%) were subtyped as low risk luminal A by Mammaprint/BluePrint despite demonstrating high risk clinicopathologic features including larger size (average 2 cm vs overall average 1.4 cm), higher grade (1 low grade, 11 intermediate grade, and 1 high grade vs totals of 36 low grade, 42 intermediate grade, and 20 high grade), and increased proliferation indices. 3 (15%) of discordant cases revealed HER2 amplification by fluorescence in situ hybridization. Near complete agreement was found among basal subtype and Luminal A tumors with Ki-67 less than 12%, indicating the lack of added value among these cases. Conclusion: Study results validate the limited role of MammaPrint/BluePrint in cases of invasive breast cancer. Specifically, the greatest value of MammaPrint/BluePrint was recognized in luminal subtypes with intermediate grade and proliferation indices ranging from 12 – 29%. Citation Format: Cross AW, McEvoy JR. An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-09.

Abstract P1-06-04: Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading?

Abstract Histological grade remains an independent predictor of outcome for invasive breast cancer. The internationally accepted standard grading system is the Elston and Ellis grading system based on a local hospital (Nottingham) cohort treated between 1951-1973. Histological grade, with nodal status, tumour size and receptor measurements (ER, PgR, HER2) give important information even in the context of current molecular testing for breast cancer. In 2009 we proposed a simplified approach to the EE system based on evidence from another hospital series (Thomas et al Histopathology 2009 DOI 10.1111/j.1365-2559.2009.03429.x). Here we report a second validation of this approach using a large phase III clinical trial cohort the Tamoxifen Exemestane Adjuvant multicentre Trial. A single pathologist (EM) regraded over 4200 cases using a single H&amp;E slide from the TEAM pathology study. Individual scores (1-3) were provided for tubule formation, nuclear pleomorphism and mitotic count and summed to provide the EE score (3-9) resulting in a final grade of 1, 2 or 3 for each case. As previously reported the Simplified Binary Scoring system (SBS) reorganizes this data such that each component is given a score of 1 or 2 with a sum ranging from 3-6. In the current analysis we compared the impact of this revised grading system on patient outcome. Of 4264 centrally regraded tumours in the TEAM pathology cohort, EE scores for tubular formation were 1 in 102 cases (2.4%), 2 in 503 cases (11.8%) and 3 in 3659 (85.8%). For nuclear pleomorphism only 2 cases were EE score 1 (0.05%), 3117 were score 2 (73.1%) and 1146 score 3 (26.9%). For Mitotic count 3423 (80.3%) were scored 1, 707 (16.6%) scored 2 and 134 scored 3 using the EE system. As previously observed, most/all EE categories could be captured using a simple binary system (SBS, see Table 1). Table 1 EE Grade SBS SCORE12335460043239705068217600618 GG Score EE GradeLowHigh 13327819.02%21377132248.98%35751790.07% GG Score SBS SCORELowHigh 33508419.35%4120284741.34%515947474.88%65751289.98% In a comparison between conventional grading and molecular (using a Genomic-Grade signature) we observed the predicted equal split of EE Grade 2 cases into GG high/versus low. For the SBS score the higher scores were enriched for GG High cases. We show a novel grading system can provides a potentially simple and more reproducible approach to immunohistochemical grading. Comparisons with molecular grading approaches may suggest improved concordance between novel grading approaches and molecular systems. Further comparisons with outcome and molecular signatures will be presented. Citation Format: Bartlett JMS, Thomas J, Mallon E, Piper T, Bayani J, Hasenburg A, Kieback DG, Markopoulos C, Dirix L, Seynaeve C, van de Velde CJH, Rea DW. Simplified histological grading of breast carcinoma – potential for improved concordance and consistency in breast cancer grading? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-04.

Evaluation of Bevacizumab for the Treatment of Epidural Fibrosis by Immunohistochemical Staining for CD105 and Osteopontin.

To evaluate bevacizumab for epidural fibrosis (EF) treatment in an experimental rat model using histopathology as well as immunohistochemical staining for CD105 and osteopontin (OPN). Sixteen Wistar Albino rats underwent either laminectomy alone to induce EF (group I, control) or laminectomy plus local bevacizumab treatment (group II). The degree of EF was compared between groups using the current histopathological grading method as well as immunohistochemistry for CD105 and OPN. In addition, the consistency of EF staging using CD105 and OPN expression was compared to that using histopathology. The grade of EF was significantly lower in group II than in group I based on the fibroblast count and fibrosis density determined using histopathology, as well as by CD105 expression determined using immunohistochemistry. In contrast, OPN expression was not a reliable marker for EF evaluation because it did not show a significant difference between the two groups. Bevacizumab prevents EF development as assessed using both histopathology and CD105 expression. CD105 is a potentially reliable marker for the immunohistochemical grading of EF, in contrast to OPN.

Molsidomine (MOL) reducespostoperative pelvic adhesion: A rat uterine horn model

Aim: Postoperative pelvic adhesions (PPAs) are a common complication that leads to many problems. This study aimed to compare the role of Seprafilm (a protective barrier), and molsidomine (MOL), recognized for its antioxidative and antiproliferative effects, in preventing pelvic adhesion. Material and Methods: A total of 30 of female Wistar albino rats were randomly divided into 3 groups. They underwent bilateral uterine horn injury. The rats in the Sham group (n=10) received no special treatment. The rats in the Seprafilm group (n=10) were treated withSeprafilm. The rats in the MOL group (n=10) received 10 mg/kg MOL orally for 14 days. Adhesion scores were evaluated using macroscopic, microscopic, and immunohistochemical grading 14 days postoperatively. Results:The Majuzi adhesion score of the rats in the MOL group [1 (0-4)] was lower than the score of the rats in the sham [4 (2-5)] and Seprafilm [4 (1-5)] (p

Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.

Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are <40years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value=0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value=0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value=0.0001). No significant associations between cyclin D1 immunohistochemical staining and grade, recurrence and alive status were observed. Significant different survival distributions were observed (P-value=0.011) and poor survival behavior was correlated with negative cyclin D1 immunohistochemical staining. In conclusion, greater frequency of cyclin D1 expression was revealed in normal endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients.

Chemotherapy-induced Sinusoidal Injury (CSI) score: a novel histologic assessment of chemotherapy-related hepatic sinusoidal injury in patients with colorectal liver metastasis

BackgroundPreoperative neoadjuvant therapy for colorectal liver metastases (CRLM) is increasing in use and can lead to chemotherapy-induced damage to sinusoidal integrity, namely sinusoidal obstruction syndrome (SOS). SOS has been associated with an increased need for intraoperative blood transfusions, increased length of hospitalization post-surgery, decreased tumor response, and a shorter overall survival after resection due to liver insufficiency. It is critical for clinicians and pathologists to be aware of this type of liver injury, and for pathologists to include the status of the background, non-neoplastic liver parenchyma in their pathology reports. In this study, expression of CD34 by sinusoidal endothelial cells (SECs), increased expression of smooth muscle actin (SMA) by hepatic stellate cells (HSCs), and aberrant expression of glutamine synthetase (GS) by noncentrizonal hepatocytes were semiquantitatively evaluated in liver resection or biopsy specimens from patients with CRLM to determine their diagnostic value for assessing chemotherapy-induced sinusoidal injury (CSI).MethodsThe expression of each marker was compared among 22 patients with CRLM with histologically evident SOS (SOS+) and 8 patients with CRLM who had not undergone chemotherapy. Each case was given a histologic grade using the sinusoidal obstruction syndrome index score (SOS-I) to assess the likelihood of SOS. Cases were also given an immunohistochemical grade using the total CSI score calculated as the sum of CD34, SMA, and GS scores.ResultsAbnormal staining patterns for CD34 and SMA were significantly more frequent and extensive in SOS+ cases than in the controls (81.8% vs. 25%, P < 0.01; 72.7% vs. 25%, P = 0.03). Aberrant GS expression in midzonal and periportal hepatocytes was only observed in SOS+ cases (31.8% vs. 0%), but this difference did not reach statistical significance. The CSI score was significantly higher in the SOS+ cases when compared to controls (P < 0.01), and was associated with a higher SOS histologic grade (P = 0.02).ConclusionsThe CSI score, calculated using an immunohistochemical panel consisting of CD34, SMA, and GS, may serve as an objective marker of chemotherapy-induced sinusoidal injury and could help diagnose this peculiar form of liver injury.