Histopathological Prognostic Factors Research Articles

POORLY DIFFERENTIATED CLUSTERS IN COLORECTAL CARCINOMA: ASSOCIATION WITH OTHER HISTOPATHOLOGICAL PROGNOSTIC PARAMETERS INCLUDING TUMOUR BUDDING

Objective: In India, colorectal carcinoma (CRC) ranks third in terms of cancer incidence. Pathologists are essential when it comes to determining the stage, examining surgical margins, and recording the histopathologic prognostic factors. A new prognostic grading system is proposed named poorly differentiated clusters (PDCs), which are defined by neoplastic clusters of 5 cells lacking glandular structure in the invasive front of the stroma. It is significant for cancer-specific and recurrence-free survival in CRC patients, reflecting the biological aggressiveness of the tumor. Aim of the study was to analyse of PDCs in colorectal carcinomas and association with other histopathological prognostic factors. Methods: The Hematoxylin and Eosin (HandE)-stained slides of 76 histopathologically diagnosed CRC resection specimens were reviewed. Poorly differentiated clusters (PDC) were assessed into under 200x power. The correlation of PDC with other histopathological prognostic parameters like tumor size, site, grade, laterality, lymphovascular invasion, perineural invasion, T stage, N stage, and tumor budding was analyzed using descriptive statistics and the Chi-square test with SPSS version 26.0. Results: There was no significant association between PDC and age, tumor location, tumor size, histological grade, LVI, PNI, or lymphnode status. Where a significant association was noted between the sex and PDC grade (P value = 0.035), T stage and PDC grade (P value = 0.045), and N stage and PDC grade is significant (P value = 0.001). Conclusion: PDCs may be considered, along with other clinical-pathological parameters, a promising prognostic factor for the management of patients with CRC and should be included in pathological reports, but it still needs standardization and further validation. At the same time, tumor budding can become an irreplaceable histological indicator for identifying a high malignant potential carcinoma and poor prognosis in CRCS, thus indicating the need for aggressive postoperative management to improve the prognosis of the patient. PDC is important for the survival of CRC patients, indicating the aggressiveness of the tumor both in terms of cancer-specific survival and freedom from recurrence. PDC may help to identify patients who need a more intensive postoperative follow-up and the possibility of adjuvant therapy.

Histopathological Prognostic Factors of Surgically Treated HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is rising in prevalence and is associated with better survival than HPV-negative OPSCC. In surgically treated HPV-negative OPSCCs, adverse pathologic features such as positive surgical margins, extra-nodal extension (ENE) and perineural invasion are well described to portend worse clinical outcomes. These adverse pathological features, however, are not validated prognostic markers among surgically treated HPV-positive OPSCCs. To that end, we pooled all available evidence to address the prognostic significance of these histologic features. This meta-analysis was performed according to PRISMA guidelines. PubMed, Web of Science and Embase databases were systematically searched for articles evaluating 13 known adverse histopathological prognostic factors of surgically treated HPV-associated OPSCC. Data analysis was done using R v4.0.5. A total of 32 studies (n = 31,535) fulfilled the inclusion criteria. ENE and advanced pT stage were associated with poorer overall survival (OS) [hazard ratio (HR):1.80, 95% confidence interval (CI) [1.59-2.03], p < 0.0001, HR: 3.28, 95% CI [2.20-4.87], p = 0.0025]; disease-specific survival (DSS) (HR: 3.14, 95% CI [1.20-8.26], p = 0.0327, HR: 3.49, 95% CI [2.45-4.96], p = 0.0043) and disease-free survival (DFS) (HR: 2.03, 95% CI [1.05-3.94], p = 0.0397, HR: 3.66, 95% CI [2.81-4.77], p = 0.0001) respectively. The presence of lymphovascular invasion (HR: 1.46, 95% CI [1.22-1.75], p = 0.0018) and positive margins (HR: 1.50, 95% CI [1.185-1.899], p = 0.0069) significantly worsen OS. ENE, advanced pT stage, positive margins and lymphovascular invasion were adverse histologic prognostic marker among surgically treated HPV-positive OPSCC. The presence of these factors should be carefully evaluated in order to select the optimal patients for surgical treatment.

Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.

Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.

The association between variant histology and prognostic, histomorphological and clinical aspects of bladder urothelial carcinoma

This study underscores the imperative consideration of histological subtypes and divergent differentiation in accurately estimating bladder urothelial carcinoma prognosis and guiding treatment decisions. A comparative analysis was conducted, examining clinical, histological, and prognostic factors between conventional urothelial carcinoma and urothelial carcinoma with variant histology in a clinical sample. A retrospective analysis of slides and other clinicopathologic data was conducted these cases, with an emphasis on key diagnostic elements. We examined 829 cases of urothelial carcinoma of the bladder, comprising of 744 transurethral resection (TUR) and 85 radical cystectomy (RS) specimens, an analysis that showed that 80.5 % (667 cases) were conventional urothelial carcinoma (CUC) and that 19.5 % (162 cases) exhibited variant histology (hereafter “urothelial carcinoma with subtype histology” [UCSH]). TNM classifications for the RS cases were as follows: 2 cases were stage group 0a, 11 stage group 1, 16 stage group 2, 45 stage group 3a, 2 stage group 3b, 1 stage group 4a, and 8 stage group 4b. Only 2 of the RS cases were found to be non-invasive. Among 744 TUR specimens, 387 were found to have a non-invasive tumor whereas 357 had invasive tumors. The most prevalent subtype in the UCSH group was urothelial carcinoma with squamous differentiation, accounting for 54.3 % (88 cases). Notably, 8.02 % (13 cases) exhibited more than one histological subtype. Papillary configuration, histological grade, lamina propria, muscularis mucosa and serosa invasion, lymphovascular invasion, presence of urothelial carcinoma in situ, and overall survival significantly differed between the UCSH and CUC groups (p < 0.05). However, mean age, gender, tumor size, lymphocytic response, disease-free survival, and survival status did not differ significantly (p > 0.05). Among the UCSH group, lower levels of papillary configuration, higher histological grade, higher degree of lamina propria, muscularis mucosa and serosa invasion, and the presence of carcinoma in situ corresponded to higher percentage of histological subtype morphology (p < 0.05). No significant difference in survival status was observed between the groups with and without subtype histology (p = 0.083). This study found that clinical and histopathological prognostic factors associated with a more aggressive disease were linked to the presence and percentage of histological subtypes. Recognizing histological subtype is crucial for treatment decisions and prognosis prediction in urothelial carcinoma cases with these subtypes.

Copy Number Alteration of Cyclin D1 (CCND 1) Gene as a Prognostic Factor in Oral Squamous Cancers and its Correlation with Immunohistochemistry (IHC)

Background Oral squamous cancers remain the most common cancers among males in India and the third most common cancer among men and women combined, with an age standardized ratio of 9.1 per 100,000 population. Surgery and chemoradiation have not improved survival rates significantly and hence, newer therapeutic targets are needed. Cyclin D1 (CCND1) is a proto-oncogene which is located on chromosome 11q13 and has been found to be amplified in many cancers including oral cancers. It is said to correlate with aggressive tumor growth and a poorer prognosis. Aim This article correlates cyclin D1 (CCND1) gene copy number alteration with clinicopathologic prognostic factors in oral squamous cancers. Materials and Methods Sixty-three patients who underwent surgery for oral cancer between January and June 2022 were included in the study after obtaining informed consent and ethics approval. Copy number alteration of CCND1 was assessed using quantitative polymerase chain reaction (Qf PCR) and correlated with clinical and histopathological prognostic factors, including short-term recurrence. Statistical analysis was performed using the SPSS software. Results A statistically significant correlation was determined between the Qf PCR values of CCND1 gene and locoregional recurrence. Gene copy number alteration also correlated strongly with a higher grade of the primary tumor. There was also a significant correlation between the Qf PCR values and the immunohistochemistry for cyclin D1. Conclusion Cyclin D1 offers a new therapeutic target in oral cancers and may improve survival without significant treatment-related morbidity.

The contrast-free diffusion MRI multiple index for the early prediction of pathological response to neoadjuvant chemotherapy in breast cancer.

Early tumor response prediction can help avoid overtreatment with unnecessary chemotherapy sessions. It is important to determine whether multiple apparent diffusion coefficient indices (S index, ADC-diff) are effective in the early prediction of pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). Patients with stage II and III BCs who underwent T1WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI using a 3 T system were included. They were divided into two groups: major histological responders (MHRs, Miller-Payne G4/5) and nonmajor histological responders (nMHRs, Miller-Payne G1-3). Three b values were used for DWI to derive the S index; ADC-diff values were obtained using b = 0 and 1000 s/mm2. The different interquartile ranges of percentile S-index and ADC-diff values after treatment were calculated and compared. The assessment was performed at baseline and after two and four NAC cycles. A total of 59 patients were evaluated. There are some correlations of interquartile ranges of S-index parameters and ADC-diff values with histopathological prognostic factors (such as estrogen receptor and human epidermal growth factor receptor 2 expression, all p < 0.05), but no significant differences were found in some other interquartile ranges of S-index parameters or ADC-diff values between progesterone receptor positive and negative or for Ki-67 tumors (all P > 0.05). No differences were found in the dynamic contrast-enhanced MRI characteristics between the two groups. HER-2 expression and kurtosis of the S-index distribution were screened out as independent risk factors for predicting MHR group (p < 0.05, area under the curve (AUC) = 0.811) before NAC. After early NAC (two cycles), only the 10th percentile S index was statistically significant between the two groups (p < 0.05, AUC = 0.714). No significant differences were found in ADC-diff value at any time point of NAC between the two groups (P > 0.1). These findings demonstrate that the S-index value may be used as an early predictor of pathological response to NAC in BC; the value of ADC-diff as an imaging biomarker of NAC needs to be further confirmed by ongoing multicenter prospective trials.

The Prognostic Value of Histopathological Features in Early-Stage Mycosis Fungoides: Insights from a Retrospective-Prospective Cohort Study.

Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective-prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte "keepers" significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.

Lympho-vascular invasion in oral cavity cancers – A bridge between tumour biology and clinical outcomes

ObjectiveVarious histo-pathological prognostic factors have been identified in oral cavity squamous cell carcinomas (OCSCC). One such factor is the status of lympho-vascular invasion (LVI). We carried out this analysis to evaluate the association of LVI with other prognostic factors and the clinical outcomes. MethodsData of patients with OCSCC who underwent curative intent surgery from January-2017 to December-2019 at our institute were retrospectively evaluated. The association of LVI with various tumour-node related prognostic factors and its effect on overall and disease-free survival (OS, DFS) were analyzed. Resultsof the total 234 patients, 71 % (166) had Bucco-alveolar-complex primary. 62.8 % (147) had locoregionally advanced disease. 91.5 % (214) required adjuvant treatment.The LVI positivity was 77.4 %, 63.3 % in tumour size >3cm/<3 cm, 85 %, 59.7 % in depth of infiltration >1cm/<1 cm, 82.4 %, 57.6 % in T3-T4/T1-2, 91.9 %, 59.9 % in grade 3/others and 96.8 %, 13.8 % in perineural invasion present/absent, respectively (p < 0.05). In the presence of LVI, lymph node positivity was 60.6 %, N2–N3 were 41.9 % and extra-capsular extension was 26.9 % as compared to LVI negative – 5.4 %, 5.4 % and 4.1 % respectively (p < 0.05).With median follow up of 37.3 months, 2year OS and DFS were 76.6 % and 75.5 % respectively. The 2year OS and DFS for the LVI-positive group were 70.4 % and 69.3 % compared to 90.6 % and 89.3 % for LVI-negative (p = 0.00). Loco-regional and distal (any) recurrence was seen in 20.9 % (49) and 7.3 % (17), the same for LVI-positive was 25.6 % (41) and 10 % (16) compared to 10.8 % (8) and 1.4 % (1) for LVI-negative (p < 0.05). ConclusionIn oral cavity cancers, there is positive association of LVI with various tumour-node related prognostic factors and clinical outcomes.

Vascularization of choroidal melanomas as a prognostic factor: Comparative analysis between color Doppler and histopathological aspects of tumors

Objectives: The objective of the study was to correlate color Doppler with the vascularization of choroidal melanoma (CM) observed in histopathological sections and also to analyze the vascular histopathological prognostic factors of these tumors. Patients, Materials, and Methods: This was an experimental, cross-sectional, and analytical study carried out at Escola Paulista de Medicina - UNIFESP (São Paulo) and at the Ocular Pathology and Translational Research Laboratory of McGill University (Montreal/Canada). Twenty-five enucleated eyes of patients with CM were studied, 10 patients studied at UNIFESP and 15 patients studied at McGill University. The first 10 patients (Brazil), before enucleation, were submitted to color Doppler, all performed at UNIFESP. The resistance index (RI) and maximum systolic velocity of each tumor were calculated. The inclusion criteria of this study were as follows: CMs &gt;8 mm in thickness, enucleation as primary treatment, histopathological blocks sufficient for hematoxylin–eosin staining, periodic acid–Schiff, and CD34 immunohistochemistry. Exclusion criteria included tumors smaller than 8 mm and/or previous treatments such as laser or brachytherapy. Regarding the histopathology of each CM, cell-type classification, vessel diameter measurements, count of the number of mitoses, and vascular clefts were carried out. The latter are considered vessels because they are lined by endothelium (CD34 positive) and surrounded by melanoma cells. Results: There was a statistical correlation between RI and cell type (P &lt; 0.05). Tumors with a better prognosis (spindle cell) showed higher RI compared to epithelioid tumors, with a worse prognosis. The number of mitoses and vascular clefts correlated with the cell type, with a statistically significant difference (P &lt; 0.001). Tumors of worse prognosis (epithelioid) showed an increase in the number of mitoses and in the number of vascular clefts. There was no difference between vessel diameter and cell type. Conclusions: The number of vascular clefts has a positive prognostic correlation with the malignancy of CM. Doppler RI showed a positive prognostic correlation with CM malignancy. For the first time, the usefulness of vascular clefts as prognostic factors was proven, and a new classification of the vascular network in CMs was proposed.

Low nuclear expression of HIF-hydroxylases PHD2/EGLN1 and PHD3/EGLN3 are associated with poor recurrence-free survival in clear cell renal cell carcinoma.

Hypoxia inducible factors, HIF-1α and HIF-2α, and their main regulators, the prolyl hydroxylase domain proteins (PHDs), mediate cellular response to hypoxia and contribute to tumor progression in clear cell renal cell carcinoma (ccRCC). These biomarkers may improve the value of traditional histopathological features in predicting disease progression after nephrectomy for localized ccRCC and guide patient selection for adjuvant treatments. In this study, we analyzed the associations of PHD2 and PHD3 with histopathological tumor features and recurrence-free survival (RFS) in a retrospective cohort of 173 patients who had undergone surgery for localized ccRCC at Helsinki University Hospital (HUH), Finland. An external validation cohort of 191 patients was obtained from Turku University Hospital (TUH), Finland. Tissue-microarrays (TMA) were constructed using the primary tumor samples. Clinical parameters and follow-up information from 2006 to 2019 were obtained from electronic medical records. The cytoplasmic and nuclear expression of PHD2, and PHD3 were scored based on immunohistochemical staining and their associations with histopathological features and RFS were evaluated. Nuclear PHD2 and PHD3 expression in cancer cells were associated with lower pT-stage and Fuhrman grade compared with negative nuclei. Patients with positive nuclear expression of PHD2 and PHD3 in cancer cells had favorable RFS compared with patients having negative tumors. The nuclear expression of PHD2 was independently associated with a decreased risk of disease recurrence or death from RCC in multivariable analysis. These results were observed in both cohorts. The absence of nuclear PHD2 and PHD3 expression in ccRCC was associated with poor RFS and the nuclear expression of PHD2 predicted RFS regardless of other known histopathological prognostic factors. Nuclear PHD2 and PHD3 are potential prognostic biomarkers in patients with localized ccRCC and should be further investigated and validated in prospective studies.

Prognostic Value of Tumor Deposits in Patients with Colorectal Cancer.

Tumor nodules or tumor deposits (TDs) are a histopathological prognostic factor that are associated with a negative evolutionary course in patients with colorectal cancer (CRC). There are still controversial aspects of TDs, including how they should be integrated into the TNM classification system. The objective of this study was to analyze the predictive value of TDs for cancer-related survival (CRS) and time-to-recurrence survival (TTR) and to evaluate the prognostic value of TDs in patients whose tumors also presented lymph node metastasis (LNM). In this retrospective observational study, all patients treated for CRC between January 2010 and December 2020 at the same hospital were included. CRS and TTR were classified by tumor stage. The results were compared between patients whose tumors had TDs and patients whose tumors did not. A total of 1426 patients met the criteria for inclusion in the analysis. TDs were detected in 178 patients (12.5%): 60 had tumors without LNM, and 118 had LNM. Patients with TD tumors had a lower CRS at 60 months after diagnosis (42% vs. 82%; p < 0.001) and a shorter TTR (34% vs. 79%; p < 0.001). Cox multiple regression analysis revealed that the presence of TD was associated with an increased risk of death from CRC (HR: 1.820; 95% CI: 1.327-2.496) and an increased risk of recurrence (HR: 2.315; 95% CI: 1.743-3.073). In each N stage category, the CRS was significantly lower in the subgroup with TD+: in patients with N1a tumors, the CRS was 44% when TD+ vs. 70% when TD- (p = 0.019); in the N1b group it was 36% vs. 66% (p < 0.001); in the N2a group it was 34% vs. 58% (p = 0.012); and in N2b tumors it was 23% vs. 53% (p = 0.031). The present study shows that the information on the presence of TDs is complementary to that provided by LNM and allows the identification of subgroups of patients in each N stage determined by two metrics, CRS and TTR. TDs should be included in the definition of TNM system categories in patients who simultaneously present with LNM.

Breast Carcinoma: Correlation of Molecular Subtypes with Histopathologic Characteristics

Context: Breast carcinoma is a heterogenous disease and similar histological subtypes may exhibit different behavior and treatment response. The molecular classification may provide better prognostic, predictive and therapeutic information than histological classification. The study aimed at evaluating the distribution of molecular subtypes of breast cancer and its association with prognostic factors. Method: This prospective cross-sectional study was conducted on breast cancer cases, over a period of 2 years, at M.S. Ramaiah Medical College and Hospitals, Bengaluru. The resection specimens were evaluated for histopathological features. Immunohistochemical analysis for ER, PR, Her2neu and Ki-67 expression was performed to identify molecular subtypes. Correlation of molecular subtypes with histopathological prognostic factors was done by Chi- square test or Fischer’s exact test. Results: A total of 85 cases were evaluated and classified into Luminal A (50.6%), Basal like (27%), Luminal B (11.8%) and HER-2 enriched (10.6%) molecular subtypes. Invasive ductal carcinoma was the commonest histologic type across all the molecular subtypes. Majority of low-grade tumors were Luminal A and most of high-grade tumors were Basal like (p= 0.004). HER-2 enriched and Basal like tumors were relatively more frequent in ≤ 50 years of age and Luminal A tumors exhibited less frequent lymph node metastasis. However, these associations fell short of statistical significance. Conclusion: Luminal A tumors are the most common molecular subtype. Statistically significant correlation exists between histologic grade and molecular subtype. There is no significant correlation between molecular subtype and age, tumor size, nodal metastasis, pathological T stage and TNM stage. Keywords: Basal like, Breast carcinoma, HER2­Enriched, Luminal A, Luminal­ B, Molecular subtypes

Histopathological prognostic factors in post NACT ovarian cancers: A retrospective study

Epithelial ovarian carcinoma is the most common type of all the ovarian cancers. The patients with advanced stage are initially treated with neo-adjuvant chemotherapy followed by interval debulking surgery. The high mortality rate is mainly due to advanced stage disease at initial presentation. This a retrospective study carried out in department of pathology at Bhagwan Mahaveer cancer hospital, Jaipur. The retrospective cases data was collected and analyzed from patient records on basis of inclusion and exclusion criteria.: Patients of advanced ovarian cancer with fibrosis grade 3, necrosis grade 2, presence of psammoma bodies, presence of collagen deposition, low Ki67 index, positive ER status were associated with longer DFS (p value= 0.014,0.029,0.033,0.028,0.001 and 0.001 respectively) and OS (P value 0.025,0.005,0.002,0.015,0.001 and 0.001 respectively).We propose that the prognostic histopathological parameters analysed in our study in post NACT patients of ovarian carcinoma should be reported in final histopathological report, as these factors can provide an extra tool for clinicians to optimize patient management and care.

Digital and manual interfollicular Ki-67 are associated with a progression-free survival in patients with low-grade follicular lymphoma.

Novel histopathologic prognostic factors are needed to identify patients with follicular lymphoma (FL) at risk of inferior outcomes. Our primary objective was to evaluate the Ki-67 proliferative index in follicular and interfollicular areas in tissue biopsy specimens from patients with newly diagnosed FL and correlate with clinical outcomes. Our secondary objective was to correlate PD-L1 and LAG-3 with clinical outcomes. Seventy cases of low-grade FL from the University of Minnesota were evaluated with Ki-67 immunohistochemical stain. Ki-67 expression as a continuous variable was interpreted digitally and manually in follicular and interfollicular areas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Cox regression, and hazard ratios (HRs) per 10-point increase in Ki-67 were calculated. Progression-free survival at 4 years was 28% (95% CI, 19%-41%). Interfollicular, but not follicular, Ki-67 was associated with PFS by manual (HR, 1.33; P = .01) and digital (HR, 1.38; P = .02) analysis. Digital and manual Ki-67 were only moderately correlated but demonstrated similar effects on PFS. At 4 years, OS was 90% with no association with follicular or interfollicular Ki-67 proliferation. Higher interfollicular Ki-67 by either digital or manual analysis is associated with a poorer PFS in patients with low-grade FL. These results suggest further validation of this marker is warranted to improve pathologic risk stratification at FL diagnosis. PD-L1 and LAG-3 were not associated with PFS or OS.

Assessment of Immunohistochemical Expression of Androgen Receptor and its Correlation with Histopathological Prognostic Factors in Prostatic Carcinoma

Assessment of Immunohistochemical Expression of Androgen Receptor and its Correlation with Histopathological Prognostic Factors in Prostatic Carcinoma

Adjuvant External Beam Radiotherapy and Histopathologic Prognostic Factors in Tall Cell Papillary Thyroid Carcinoma

Differentiated thyroid cancer is a diverse disease, with histopathologic characteristics contributing to prognosis and treatment decisions. Tall cell variant of papillary thyroid cancer (TCV-PTC) carries a poor prognosis relative to other histologies, with first site of failure most often in the neck. Several small studies suggest there may be a disease control benefit to adjuvant external beam radiotherapy (EBRT) for certain high-risk DTC populations; however, data is limited. In this study we aim to shed light on both histopathologic prognostic factors and survival outcomes of patients with TCV-PTC carcinoma treated with surgery followed by EBRT and Radioactive Iodine (RAI) or RAI alone. We hypothesize that EBRT with RAI leads to better disease control than RAI alone. Patients with TCV-PTC diagnosed between 1997-2020 at a single institution were included in the analysis. TNM staging was standardized to AJCC 8th edition. Demographics, staging, and histologic characteristics were compared between the two treatment groups using T-tests and Fisher's exact tests. Kaplan-Meier survival analyses were performed between patients receiving EBRT vs. RAI alone for disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS), along with Cox Proportional Hazards analysis. A total of 93 patients were included. Of these patients, 22 received adjuvant RAI and EBRT, and 71 received RAI alone. There was no statistical difference in race, gender, tall cell percentage in the pathology specimen, TNM stage, AJCC group stage, or disease recurrence in patients receiving EBRT vs. RAI alone. However, those receiving EBRT were significantly older (RAI mean age (SD): 50.6 (18.7), EBRT mean age (SD): 59.7 (14.4), p = 0.02) and length of follow-up was shorter for the EBRT cohort (RAI mean (SD): 8.80 (5.81) years, EBRT mean (SD): 4.53 (2.14) years, p < 0.01). Multifocal disease (HR: 3.04, 95% CI: 1.30 - 7.08, p = 0.01) and soft tissue invasion (HR: 2.93, 95% CI: 1.28 - 6.75, p = 0.01) were associated with decreased DFS, whilst age (HR 1.08, 1.01 - 1.15: p = 0.03) was associated with decreased CSS; tall cell percentage in the pathology specimen, extra-thyroidal extension, vascular invasion, and positive surgical margin were not significant for either metric. There was no statistical difference in DFS (p = 0.5), CSS (p = 0.3), or OS (p = 0.6) between patients that received EBRT and RAI vs. RAI alone. DFS, CSS, and OS were not different between patients who received EBRT compared to RAI only in this high-risk subgroup of patients. Short interval follow-up for the EBRT group and significant age differences between the EBRT and RAI cohorts may confound results. Given the significant association of advanced age with CSS, an expanded, age-matched cohort analysis is underway.

Prognostic Factors for Relapse in Patients With Clinical Stage I Testicular Seminoma: A Nationwide, Population-Based Cohort Study.

Approximately 20% of patients with clinical stage I seminoma relapse. Tumor size and rete testis invasion have been identified as risk factors for relapse. However, the level of evidence supporting the use of these risk factors in clinical decision making is low. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We assessed prognostic factors for relapse in an unselected nationwide population-based setting with centralized pathology review. Patients with clinical stage I seminoma diagnosed from January 2013 to December 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histologic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified potential clinical and histopathologic prognostic factors and relapse was assessed by the use of Cox regression analysis. Of 924 patients included, 148 (16%) patients relapsed during a median follow-up of 6.3 years. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated preorchiectomy levels of β-human chorionic gonadotropin and lactate dehydrogenase were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors to 62% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the prognostic model had an overall concordance statistic of 0.70. The provided prognostic factors could replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies.

Analysis of Histological Prognostic Factors in Colorectal Carcinoma and Relationship of VEGF and E-Cadherin Expression in Prognostic Assessment

Colorectal carcinomas (CRC) are associated with several histopathological and molecular factors of prognostic and hence therapeutic implications, including for epithelial mesenchymal transition (EMT) and angiogenesis. Downregulation of E-cadherin is a crucial step in EMT, directly related to tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) induces angiogenesis and thereby tumour progression and metastases. Our objective was to analyse VEGF and E-cadherin expression in patients with CRC and to effectively assess the relationship of these with histopathological factors. 50 cases of CRC obtained over eighteen months duration, were included in the study. Haematoxylin and Eosin-stained sections were studied for histopathological factors. Immunohistochemistry with E-Cadherin and VEGF were performed on representative sections and evaluated. Histopathological features of importance noted were low grade tumour budding (55.5%), Infiltrative invasive front (83%), lympho-vascular invasion (50%). Preserved expression of E-Cadherin was seen in 66% of the cases, and 34% reduced expression, predominantly noted in patients above the age of 50, increased tumour size, mucinous variants, advanced TNM stage, lymph node involvement and high-grade tumour budding. VEGF staining was seen in 64% of the cases with varying intensity. Increased VEGF expression was noted in poorly differentiated tumours, advanced Duke’s stage and with lymph node metastasis. Colorectal carcinomas with high grade tumour budding were associated with lymph vascular invasion, infiltrative invasive front and significantly correlated with TNM stage. High grade tumours and adverse histopathological prognostic factors revealed a reduced E-cadherin expression and increased VEGF expression.

Melanoma and subcutaneous adipose tissue: Role of peritumoral adipokines in disease characterization and prognosis.

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

The Utility of Quantitative Parameters of Shear-Wave Elastography to Predict Prognostic Histologic Features of Breast Cancer.

In this study, we aimed to investigate the correlation of stiffness values of shear-wave elastography (SWE) and histopathological prognostic factors in patients with breast cancer. Between January 2021 and June 2022, SWE images of 138 core-biopsy proven breast cancer lesions from 132 patients were retrospectively reviewed. Histopathogic prognostic factors, including tumor size, histologic grade, histologic type, hormone receptor positivity, human epidermal growth factor receptor (HER2) status, immunohistochemical subtype and Ki-67 index were documented. Elasticity values including mean and maximum elasticity ( Emean and Emax ) and lesion-to-fat ratio ( Eratio ) were recorded. The association between histopathological prognostic factors and elasticity values were assessed using Mann-Whitney U and Kruskal-Wallis test, and multiple linear regression analysis. Tumor size, histological grade, and Ki-67 index were significantly associated with the Eratio ( P < 0.05). Larger tumor size and higher Ki-67 index also showed significantly higher Emean and Emax values ( P < 0.05). However, hormone receptor positivity, HER2 status, and immunohistochemical subtype were not significantly associated with elasticity values ( P > 0.05). Multivariate logistic regression analysis revealed that tumor size was significantly associated with Emean , Emax , and Eratio values ( P < 0.05). A high Ki-67 index was also significantly associated with high Eratio values. Larger tumor size and higher Ki-67 index are independently associated with high Eratio values. Preoperative SWE may improve the performance of conventional ultrasound in predicting prognosis and treatment planning.