Histopathological Variables Research Articles

Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis

Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Diffusion tensor imaging of vastus lateralis in patients with inflammatory myopathies.

Inflammation in patients with myositis would increase diffusion of water molecules across sarcolemma that could be detected with the help of diffusion tensor imaging (DTI). We aimed to determine an association between DTI of vastus lateralis (VL) and histopathological findings in cases of myositis and to estimate diagnostic performance of different MRI variables in predicting histopathological outcomes. This prospective cross-sectional observational study included 43 patients with myositis. MRI of bilateral thighs with DWI/DTI protocol was performed in all the patients. Thirty-three patients further underwent biopsy of right VL muscle. Imaging analysis included grading of "Muscle oedema" based on signal intensity (SI) and extent and "fatty infiltration" based on extent on conventional sequences and, acquiring DWI and DTI parameters. Gold standard method to determine inflammation in muscles was histopathological examination. Comparison of DTI/DWI variables with clinical and histopathological variables was done. The average DWI apparent diffusion coefficient (ADC) and DTI ADC values in the patients were 1.77 ± 0.35 and 2.06 ± 0.35 respectively. The average functional anisotropy (FA) was 0.39 ± 0.17 and, the 3 eigenvalues in the patients were 2.96 ± 0.63, 2.05 ± 0.32, and 1.20 ± 0.39 respectively. VL oedema SI weighted score was the best parameter for predicting effaced fascicular architecture and marked lymphocytic inflammation in endomysium on histopathology. VL fatty infiltration weighted score was the best parameter in predicting perifascicular atrophy. Addition of DWI or DTI didn't add significantly in determining active inflammation in cases of myositis.

Can intra-articular daidzein injection reduce oxidative damage and early osteoarthritis in a rabbit temporomandibular joint model?

BackgroundOxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs.MethodsThe predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations.ResultsThere were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007).ConclusionsAn intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA.

Combination of single-source dual-energy computed tomography (CT) parameters and extracellular volume fraction for predicting lymphovascular and perineural invasion in colorectal cancer.

Lymphovascular invasion (LVI) and perineural invasion (PNI) are important histopathological variables that are directly related to the survival and recurrence of patients with colorectal cancer (CRC). Preoperative prediction of LVI and PNI status in CRC is helpful in selecting patients requiring appropriate adjuvant therapy and evaluating prognosis. This study aimed to investigate the value of combining single-source dual-energy computed tomography (ssDECT)-derived parameters with extracellular volume (ECV) fraction for preoperative evaluation of LVI and PNI in CRC. This retrospective study included patients with CRC who underwent contrast-enhanced ssDECT. All diagnoses were confirmed through histopathology, and the patients were classified into positive and negative groups based on the presence of LVI/PNI. Clinical data were collected. In the arterial (AP), venous (VP) and delayed phases (DP), the ssDECT-derived parameters were measured by two radiologists. The measurement consistency was evaluated using intraclass correlation coefficients. Differences between the two groups were analyzed using the t-test, Mann-Whitney U test, or Chi-square test. Binary logistic regression was employed to construct models incorporating multiple parameters. The diagnostic performance of various parameters or models was assessed by analyzing receiver operating characteristic curves. In total, 118 patients with CRC were included in the study. Serum carcinoembryonic antigen levels, T and N stages, and histological grades differed between the two groups (all P<0.05). The ssDECT-derived parameters in the VP and DP of LVI/PNI-positive group were higher than those of -negative group (all P<0.05). The ECV fraction in the DP of LVI/PNI-positive group was higher than that of -negative group (P=0.001). Discriminating capability analysis demonstrated that the diagnostic efficacies of the DP parameters were superior to those of the VP parameters, and the normalized iodine concentration in the DP exhibited the best performance [area under the curve (AUC): 0.750; 95% confidence interval (CI): 0.648-0.852]. The combination of ECV DP with clinical and ssDECT-derived parameters demonstrated the highest discriminative capability (AUC: 0.857; 95% CI: 0.786-0.928). ssDECT-derived parameters and ECV fraction may serve as non-invasive tools for predicting the LVI/PNI status in CRC.

Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential

The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47–103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

Learning curve and safety of the implementation of laparoscopic complete mesocolic excision with intracorporeal anastomosis for right-sided colon cancer: results from a propensity score-matched study.

Retrospective studies and randomized controlled trials support the safety of laparoscopic complete mesocolic excision (CME) for the treatment of right-sided colon cancer (RSCC). Few studies, however, examine the learning curve of this operation and its impact on safety during an implementation period. We aim to evaluate the learning curve and safety of the implementation of laparoscopic CME with intracorporeal anastomosis for RSCC. Consecutive patients undergoing a laparoscopic right colectomy with intracorporeal anastomosis for RSCC between January 2016 and June 2023 were included. Clinical, perioperative, and histopathological variables were collected. Correlation and cumulative sum (CUSUM) analyses between the operating time and case number were performed. Breakpoints of the learning curve were estimated using the broken-line model. CME and conventional laparoscopic right colectomy outcomes were compared after propensity score matching (PSM). Two hundred and ninety patients underwent laparoscopic right colectomy during study period. One hundred and eight met inclusion criteria. After PSM, 56 non-CME and 28 CME patients were compared. CME group had a non-statistically significant tendency to a longer operating time (201 versus 195min; p = 0.657) and a shorter hospital stay (3 versus 4days; p = 0.279). No significant differences were found in total complication rates or their profile. Correlation analysis identified a significant trend toward operating time reduction with increasing case numbers (Pearson correlation coefficient = - 0.624; p = 0.001). According to the CUSUM analysis, an institutional learning curve was deemed completed after 13 cases and the broken-line model identified three phases: learning (1-6 cases), consolidation (7-13 cases), and mastery (after 13 cases). The learning curve of laparoscopic CME for RSCC can be achieved after 13 cases in centers with experience in advanced laparoscopic surgery and surgeons with familiarity with this technique. Its implementation within this setting seems to be as safe as performing a conventional right colectomy.

Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Frequency of BRAF Mutations in Dysplastic Nevi, Lentigo Maligna, and Melanoma In Situ.

Background: In melanomas, mutations in the BRAF gene are common and their occurrence represents an early oncogenic event. Our goal was to determine and compare the frequency of BRAF gene mutations in dysplastic nevi (ND) and melanomas in situ (MIS), as well as whether there is a correlation between the presence of BRAF gene mutations and various anamnestic, clinical, and histopathologic variables. Methods: A total of 175 patients-106 with ND, 41 with MIS, and 28 with lentigo maligna (LM) were included in the study. DNA was extracted from tissue samples and analyzed using the competitive allele-specific TaqMan chain reaction by polymerase in real time to detect the presence of BRAF V600E and V600K mutations. The data were compared with anamnestic, clinical, and histopathological data. Results: There is a statistically significant correlation between the presence of BRAF mutation and the diagnosis of melanoma in situ (χ2 test, χ2 = 29.17, p < 0.0001). Patients with LM had a significantly lower incidence of BRAF mutations compared to patients with ND and MIS. There was a significant correlation between the presence of a BRAF mutation and tumor localization, as well as the age of the patient, but no statistically significant correlation between the presence of a BRAF mutation and sex, tumor size, or previous melanoma diagnosis. Conclusions: BRAF mutations in ND are essentially required; however, they are an insufficient oncogenic trigger for the development of melanoma. This research contributes to a better understanding of the etiopathogenesis of melanoma and the role of ND as possible precursor lesions.

Using Nomograms Wisely: Predicting Sentinel Node Positivity in Melanoma.

Four externally validated sentinel node biopsy (SNB) prediction nomograms exist for malignant melanoma that each incorporate different clinical and histopathologic variables, which can result in substantially different risk estimations for the same patient. We demonstrate this variability by using hypothetical melanoma cases. We compared the MSKCC and MIA calculators. Using a random number generator, 300 hypothetical thin melanoma "patients" were created with varying age, tumor thickness, Clark level, location on the body, ulceration, melanoma subtype, mitosis, and lymphovascular invasion (LVI). The chi-square test was used to detect statistically significant differences in risk estimations between nomograms. Multivariate linear regression was used to determine the most relevant contributing pathologic features in cases where the predictions diverged by > 10%. Of 300 randomly generated cases, 164 were deleted as their clinical scenarios were unlikely. The MSKCC nomogram generally calculated a lower risk than the MIA (p < 0.001). The highest risk score attained for any "patient" using MSKCC calculator was 15% achieved in one of 136 patients (0.7%), whereas using the MIA nomogram, 58 of 136 patients (43%, p < 0.001) had predicted risk >15%. Regression analysis on patients with >10% difference between nomograms revealed LVI (26, p < 0.001), mitosis (14, p < 0.001), and melanoma subtype (8, p < 0.001) were the factors with high coefficients within MIA that were not present in MSKCC. Nomograms are useful tools when predicting SNB risk but provide risk outputs that are quite sensitive to included predictors.

Reirradiation in head and neck squamous cell carcinoma; prognostic indicators, oncologic and functional outcomes

ObjectivesPatients with recurrent squamous cell carcinoma of the head and neck (HNSCC) have a poor prognosis and limited therapeutic alternatives. While reirradiation is feasible, it is usually associated with high treatment toxicity and is not yet considered the standard of care. Based on current NCCN guidelines, in the context of very advanced head and neck cancer (recurrent and/or persistent disease), surgical intervention is explored initially with/without adjuvants while unresectable disease is approached with radiation and/or systemic therapies. Specific and reliable prognostic indicators for both -oncologic and functional outcomes- have yet to be defined for this population. MethodsRetrospective chart review of 54 patients treated with reirradiation at a tertiary academic institution between January of 1998 and January of 2024. Only patients with non-metastatic recurrent, and second primary HNSCC were included in the series. Demographics, staging, radiation dose and technique, additional therapy, histopathologic variables, EORTC toxicity, pre- and post-treatment PEG/tracheotomy dependency and oncologic outcomes were retrieved. ResultsThe study cohort consisted of 54 patients (37 males, 17 females) with HNSCC, averaging 62.7 years in age. Initial tumors were locally advanced in over 42 % of cases, with 58 % being node-negative. The head and cutaneous regions (24.5 %) and tongue (20.8 %) were the most common tumor sites. Primary surgical resection and adjuvant radiation were performed in 47.2 % of cases, and concurrent chemotherapy was used in 40.7 %. Reirradiation was mainly for local or regional recurrence (88.9 %), often following salvage surgery (68.5 %), with a mean dose of 5623 Gy over 52.5 fractions. Positive surgical margins were present in 29.4 % of cases, and extracapsular spread in 59.5 %. No significant differences were found between the salvage surgery and definitive reirradiation groups except for tumor site (P = 0.022). Median follow-up was 52.6 months, with 27 deaths reported. Lymphovascular invasion was significantly correlated with overall survival (P = 0.017), while initial tumor T-stage and neck disease involvement were linked to local-regional control (P = 0.030 and P = 0.033, respectively). Reirradiation increased tracheotomy and PEG-tube dependency by 20 % (P = 0.011) and 23 % (P = 0.003), respectively. ConclusionsReirradiation is a feasible therapeutic alternative in recurrent head and neck SCC. Oncologic outcomes observed in this series compare favorably to most published reports. Complete response and perineural invasion were independent prognostic factors for survival and locoregional control. While no mortality directly associated with treatment was observed in this series, reirradiation had a significant impact in functional outcomes in terms of increased risk of tracheotomy and peg tube dependency. Further studies are required to define the role of this treatment in head and neck cancer.

MYB immunohistochemistry as a predictor of MYB::NFIB fusion in the diagnosis of adenoid cystic carcinoma of the head and neck

Diagnosing adenoid cystic carcinoma (AdCC) is challenging due to histopathological variability and similarities with other tumors. In AdCC pathogenesis, the cellular myeloblastosis gene (c-MYB) often exhibits a MYB::NFIB fusion from a reciprocal translocation. This study aimed to assess the predictive accuracy of MYB immunohistochemistry for detecting this translocation compared to fluorescence in situ hybridization (FISH). This study included 110 AdCC patients (1999-2017) from two Dutch head and neck centers using tissue microarrays and full slides. Median MYB expression levels by immunohistochemistry were compared based on translocation status by FISH, and differences within clinicopathological parameters were examined. An immunohistochemical cut-off was established to estimate the translocation. MYB immunohistochemistry was available in 90/110 patients, with a median expression of 27%. FISH was interpretable in 79/108 tumors, identifying MYB::NFIB fusion in 44 (56%). Among 62 patients with both MYB expression and translocation data, the fusion was present in 38 (61%). These tumors had higher MYB expression (30%) than nontranslocated tumors (6%); P = .02. A 60% MYB expression cut-off yielded 100% specificity for detecting the translocation but had no prognostic value. Although MYB protein expression alone lacks diagnostic precision, protein expression >60% predicted the MYB::NFIB fusion in all tumors.

Expression of Intracellular Galectin-8 and -9 in Endometrial Cancer.

Endometrial cancer (EC) is a common gynecological cancer worldwide. Treatment has been improved in recent years; however, in advanced stages, therapeutic options are still limited. The expression of galectins is increased in several tumor types and that they are involved in important cell processes. Large studies on endometrial cancer are still pending; Specimens of 225 patients with EC were immunohistochemically stained with antibodies for Gal-8 and Gal-9. Expression was correlated with histopathological variables. The cytosolic expression of both galectins is associated with grading and survival. Cytosolic Galectin-8 expression is a positive prognostic factor for overall survival (OS) and progression-free survival (PFS), while nuclear Gal-8 expression correlates only to OS. The cytosolic presence of Galectin-9 is correlated with a better prognosis regarding OS. Our results suggest that expression of both galectins is associated with OS and PFS in EC. Further studies are needed to understand the underlying molecular mechanisms.

Expression of p53 and ki-67 in Breast Carcinomas and Their Association with Histopathological Type, Grade, and Stage

Background &amp; objective: Recently many laboratories are evaluating the usefulness of determining p53, and Ki67 proliferation activities using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might help make treatment decisions in cancer patients, their clinical usefulness is still controversial. The present study was undertaken to see the expression of p53 and Ki-67 in breast carcinoma and their associations with histopathological variables. Methods: This cross-sectional analytical study was conducted in the Department of Pathology, in collaboration with the Department of Surgery, Rajshahi Medical College Hospital and the Department of Pathology, Bangobandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period of one and a half year from July 2018 to December 2019. Resected specimens of breast tissue, histopathologically confirmed as breast carcinoma, were the study population. Histological grading of breast carcinoma was done according to Nottingham modification of the Bloom-Richardson system, while staging was done using Tumor-Node-Metastasis (TNM) classification of malignant tumors, as recommended by the Union for International Cancer Control (UICC). The Ki67 and p53 expressions were assessed by immunohistochemistry. Based on the Ki67 labeling index (Ki67-LI), the patients were divided into two groups – Ki 67 &gt; 30% (considered as over-expressed) and ≤ 30% (considered as less expressed). Likewise, p53 immuno-expression was grouped as over-expressed (score ≤ 8) and low-expressed (score &gt; 8). The histological grade, type, and stage were then compared between patients with tumours of high and low proliferating activities to find the associations of Ki67 and p53 with tumor grade, type, and stage. Result: In the present study, almost three-quarters (74%) of the specimen of the breast had high Ki67-LI and 26% intermediate and low Ki67-LI. The p53 was found to be highly expressed in the majority (86%) of the cases. Analyses of the association of biomarkers with histological grade, stage, and type revealed that advanced-stage breast cancers (Stage-IIIA) were more likely to be associated with high Ki67-LI than the early-stage breast cancers (Stage-IIA and Stage-IIB) (p = 0.023). Poorly differentiated (G3) carcinoma also more often tends to be associated with high Ki67-LI than with low and intermediate Ki67-LI (p = 0.066). Likewise, stage IIIA tumors and poorly differentiated carcinoma were also considerably higher in the p53 over-expressed group (23.3%) than in the low p53 expression group (14.3%) (p = 0.023). Conclusion: The study concluded that a substantial proportion of breast carcinomas demonstrates high Ki67-LI. The p53 overexpression is also found in the majority (86%) of the breast carcinoma cases. Both Ki67 and p53 proliferation activities show their significant presence in high-grade and advanced-stage tumours. Ibrahim Card Med J 2023; 13 (1&amp;2): 11-18

Mechanism of Weiwei granules in the treatment of chronic active Helicobacter pylori gastritis with atrophy based on the TLR4/NF-κB/COX-2 inflammatory signaling pathway.

Our paper aimed to elucidate the mechanism of Weiwei granules in the treatment of Helicobacter pylori (Hp)-positive chronic atrophic gastritis (CAG) based on the TLR4/NF-κB/COX-2 inflammatory signaling pathway. Hp-positive CAG patients were randomized into the control group (treated with quadruple therapy) or the observation group (treated with Weiwei granules based on the control group). The clinical efficacy, Hp clearance rate, and efficacy of traditional Chinese medicine (TCM) symptoms were compared between the two groups after six months of treatment. The scores of various histopathology variables, serum levels of inflammatory factors (interleukin-6 [IL-6], interleukin-8 [IL-8], and tumor necrosis factor-alpha [TNF-α]), gastrin-17 (G-17) and motilin (MTL), pepsinogen (PG) I and PG II, as well as serum levels of gastrointestinal hormone endothelin (ET), epidermal growth factor (EGF), and calcitonin gene-related peptide (CGRP), were compared between the two groups before and after treatment. TLR4, NF-κB, and COX-2 mRNA levels were compared in gastric mucosal tissues before and after treatment in the two groups. After treatment, the clinical efficacy, Hp clearance rate, and efficacy of TCM symptoms of patients in the observation group were higher than those in the control group. After treatment, the scores of various histopathology variables, serum levels of inflammatory factors (IL-6, IL-8, and TNF-α), gastrointestinal hormones (ET and EGF), and the expression levels of TLR4, NF-κB, and COX-2 mRNA in the gastric mucosal tissues were lower and G-17, MTL, CGRP, and PG I levels were higher in the observation group than in the control group. Weiwei granules can effectively improve Hp-positive CAG patients and reduce the expression levels of TLR4, NF-κB, and COX-2.

The Receptor Tyrosine Kinase EphA2 and Integrin-linked Kinase Expression in Colorectal Cancer in Relation to the Severity of the Tumor

Abstract Background: Although colorectal carcinoma is still the second cancer-related death worldwide, the current knowledge of the prognostic profile of routine markers is still humble. This study aimed to study the receptor tyrosine kinase EphA2 and integrin-linked kinase expression in relation to the severity of the disease represented by the grade, extent of invasion, and lymph node involvement. Materials and Methods: This cross-sectional study included 87 colorectal cancer cases diagnosed between 2019 and 2022. The immunohistochemical expression and scoring of integrin-linked kinase and EphA2 was carried out and correlated to the histological variables of severity. Results: The mean age of the studied cases was 57.85 years, and approximately 56.3% of them were females. The majority of the cases were moderately differentiated carcinoma (81.61%). More than half of the patients presented in T3. No lymph-node involvement was detected in 65.52 cases. The majority of the studied cases showed negative integrin-linked kinase expression in tumor cells in the colon and lymph nodes. Even positive cases showed low scores. EphA2 marker showed higher positivity in tumor cells of the colon and lymph nodes with higher scores, but no significant correlation to the histopathological variables. Conclusion: The EphA2 marker is of higher benefit than the integrin-linked kinase and the last one is of limited prognostic role in colorectal cancer due to the very high negative and low score results.

Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015.

Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.

Meningioma recurrence: Time for an online prediction tool?

Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient's lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson's and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care. A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population. Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, CDKN2A deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas. Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas.

Abstract PO2-02-09: Pathological complete response to neoadjuvant systemic therapy and its predictive factors among early breast cancer subtypes: the emerging role of HER2

Abstract Purpose Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer (BC) is a prognostic factor for relapse-free and overall survival (OS). Despite recent therapeutic developments for early BC, there are still a significant proportion of patients who do not achieve pCR. In this study we established pCR rates in routine care and investigated possible predictive factors of pCR, including HER2 status. Methods We evaluated 980 stage I-III BC patients receiving NACT between 2013 and 2022. Patient characteristics, rates of pCR (ypT0-is ypN0), toxicities, treatment modifications and survival outcomes were recorded. Standard histopathological variables were recorded [with HER2-low status, defined as HER2 1+ on immunohistochemistry (IHC) or 2+ on IHC without in situ hybridization (ISH) gene amplification]. Overall survival (OS) and relapse-free survival (RFS) were calculated. Median follow-up time was 60.3 months (interquartile range 19.7-78.7). Results The mean age of the study population was 49.6 ± 11.2 years. 64% had stage II disease, 70.5% had grade 3 disease, and 90.5% had ductal histopathology. 34.6% had estrogen receptor (ER)-positive/HER2-negative, 27.1% had triple-negative (TN), and 38.3% had HER2-positive BC. 233 patients (23.8%) had HER2-low disease. pCR rate was 35.8% in the overall population, 16.8% in ER-positive/HER2 negative BC, 32.7% in TNBC and 55.2% in HER2-positive BC. pCR rate differed according to grade, histology, HER2 status, radiological and clinical response of disease (p &amp;lt; 0.001) and early discontinuation of NACT (p = 0.001), but not according to age, menopausal status, BRCA status, platinum use, NACT dose reduction or delays, neutrophils-to-lymphocytes, platelets-to-lymphocytes, or lymphocytes-to-monocytes ratios. OS and RFS were better following pCR [HR 0.23 (95% CI, 0.14-0.38, p &amp;lt; 0.001) and HR 0.27 (95% CI, 0.18-0.40, p &amp;lt; 0.001), respectively]. Among HER2-negative BC patients (605, 61.7% of the entire cohort), there was a trend to lower pCR rate in HER2-low compared to HER2-negative (IHC 0) BC (19.7% vs 26.3% respectively, p = 0.06). pCR rate was significantly lower in ER-positive/HER2-low compared to ER-positive/HER2-negative (IHC 0) BC (12.1% vs 20.9% respectively, p = 0.031), while no difference in pCR rates was observed in TNBC patients by HER2 status. Despite a lower rate of pCR, Kaplan-Meyer curve showed that OS was significantly better in the HER2-low BC compared to HER2-negative (IHC 0) population at 100-months follow up. Multivariable Cox-regression model in the HER2-negative BC cohort demonstrated that HER2-low status was an independent predictor of OS (HR 0.59, 95% CI, 0.39-0.89 p = 0.012). Conclusions In our real-world analysis, pCR rates are consistent with the published data. Many patients still have residual disease following NACT, predicting worse outcomes, and may benefit from further adjuvant systemic therapies. Consistent with other studies, our findings suggest a possible prognostic and predictive role of HER2-low status especially among patients with ER-positive BC. This could lay the foundations for novel therapies targeting HER2 among HER2-low cancer subtypes. Citation Format: Matilde Corianò, Nicolo M.L. Battisti, Hala Aziz, Nalinie Joharatnam Hogan, Antonino Musolino, Alistair Ring. Pathological complete response to neoadjuvant systemic therapy and its predictive factors among early breast cancer subtypes: the emerging role of HER2 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-09.

Comparison of a modified staging system with 8th edition AJCC criteria in a North American cohort of pT2/pT3 HPV-negative penile squamous cell carcinoma

The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112–7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.

The Prognostic Value of Human Papillomavirus Status in Penile Cancer: Outcomes From a Norwegian Cohort Study

IntroductionPenile squamous cell carcinoma (PSCC) can develop from human papillomavirus (HPV) infection. This study investigates if the prognostic value of the TNM stage groups or the components tumor stage (pT), grade of differentiation (Grade), lymphovascular invasion (LVI), and nodular stage (pN) depend on HPV status. Also, whether the value of tumor parameters (pT, Grade, and LVI) for predicting node-positive disease depends on HPV status was investigated. Patients and MethodsStored tumor tissue from 226 patients treated for PSCC in Western Norway between 1973 and 2023 was investigated for HPV DNA. Histopathological variables were reevaluated according to the current TNM classification. Disease course was registered from hospital records. Inclusion of an interaction term between HPV and TNM stage groups in Cox regression enabled analysis of whether cancer-specific survival (CSS) of the stage groups depended on HPV status. This was also done separately for pT, Grade, LVI, and pN. Logistic regression with interaction terms between HPV and the tumor parameters were used to investigate if their predictive value depended on HPV status. ResultsHPV DNA was detected in 43% of the tumors. Stratified by HPV status, there was no significant interaction term in the Cox regression between HPV status and TNM stage groups (P = .74). Similar results were found for pT (P = .94), Grade (P = .08), LVI (P = .91) and pN (P = .77). Moreover, there were no significant interaction terms in the logistic regression between HPV status and the tumor parameters pT, Grade, and LVI (all P > .2). ConclusionsThis study found that prognosis of the TNM stage groups and the components pT, Grade, LVI, and pN were not modified by HPV in PSCC. The value of pT, Grade, and LVI for predicting lymph node-positive disease was not affected by HPV status.