Prognostic Factor In Colorectal Carcinoma Research Articles

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.

Immunohistochemical Expression Profile of SATB2 in Colorectal Adenocarcinoma and Association with Clinicopathological Parameters

Introduction: Colorectal carcinoma is the third most common cancer worldwide. Several clinicopathological parameters act as prognostic factors in colorectal carcinoma, but only a few are helpful in predicting the treatment outcome. Therefore, there is a need for better prognostic markers which also aids in assessing treatment benefits in colorectal carcinoma patients. Special AT Rich Sequence Binding Protein 2 (SATB2) is a highly specific marker for colorectal tissue. Decreased expression of SATB2 is also associated with poor prognosis in colorectal carcinoma. Aim: To analyse the histomorphology, immunohistochemical expression profile of SATB2 and association with clinicopathological parameters in colorectal adenocarcinoma. Materials and Methods: The cross-sectional study included 84 cases of colorectal carcinoma received in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chennai, Tamil Nadu, India, in the period between April 2021 to September 2022. Both biopsy and resected specimens were included in the study. Relevant clinical data was collected. Histological diagnosis, grading and staging of the tumour was done using Haematoxylin and Eosin (H&E) slides as described and tabulated. Immunohistochemistry (IHC) for SATB2 and was done and expression profile compared with the clinicopathological parameters to assess prognostic significance. Data was analysed using software-Statistical Package for Social Sciences (SPSS, version 23.0). Results: Out of the 84 cases, 42 were biopsy and 42 resected specimens. Mean age of the patients in the study was 57.9 years. Patients were predominantly males (n=51, 60.7%) with a male:female ratio of 1.54:1. Of the 84 cases, 40.5% (n=34) had tumour located in the rectum. Majority of the cases were moderately differentiated adenocarcinoma (n=48, 57.1%). Predominantly, stage III tumours (n=33, 39.3%) were noted. Out of the tumours showing decreased expression of SATB2, 55% (n=22) were left-sided tumours, metastasis was seen in 60% (n=24 cases), 37.5% of cases (n=9) showed lymphovascular invasion, and 55% (n=22) had a stage III tumour. Conclusion: The present study results indicate that a decrease in SATB2 expression is associated with presence of lymphovascular invasion, perineural invasion, regional and distant metastasis and a higher pathological stage which signifies poor prognosis in colorectal carcinoma. These aid the physician for risk stratification of patients and enable personalised treatment choices including adjuvant chemotherapy in high-risk groups.

Utility of Prognostic Scoring System Based on Histomorphological Parameters in Lowgrade Colorectal Carcinoma

Introduction: Colorectal Carcinoma (CRC) is the third most common cancer worldwide. Percentage of gland formation is the only valid parameter for histologic grading of CRC . Tumour budding and Tumour-infiltrating Lymphocytes (TILs) are emerging prognostic factors in CRC. In recent years high grade CRC has become subject to more precise molecular grading strategies. However low grade cases show in homogenous outcome due to still insufficient categorization. The focus of this study is to determine whether the combination of amount of gland formation, budding, and TILs will allow us to further characterize large in homogenous group of WHO low-grade cases into prognostically significant subgroups. Aim: To estimate the significance of tumour budding and TILs in low-grade CRC and to categorise low-grade CRC into prognostic subgroups taking into account 3 histologic parameters-gland formation, tumour budding and TIL. Materials and Methods: This was a descriptive cross-sectional study done in the Department of Pathology, MES Medical College, Malappuram, Kerala, India. It was an ambispective study (retrospective from January 2015 to December 2021 and prospective from December 2021 to March 2022) which analysed 105 World Health Organization (WHO) low-grade CRC cases. The demographic data of the patients was collected and histopathological assessment of tumour grade, pT, pN, lymphovascular invasion (LVI), Tumour-infiltrating lymphocytes (TIL) and tumour budding (TB) was done on Haematoxylin and Eosin (H&E) stained sections. A morphology-based risk score was developed taking into account 3 parameters- percentage of gland formation, budding, and TIL. For each parameter, 1 to 2 points were given, resulting in a sum score, dividing the CRC cases into a low-, an intermediate-, and a high-risk group. Statistical analysis was performed using SPSS 25. The results were expressed as numbers and percentage. Pearson Chi-square test was used to test the relationship. Results: In the present study degree of budding significantly associated with pT stage (p=0.02), pN stage (p=0.042) and LVI (p=0.038). TIL also differed significantly with pT (p=0.001) pN (p=0.042) and LVI (p=0.004). Applying the prognostic scoring to 105 cases, 33 (31.4%) cases showed high score, 30 (28.6%) cases were of intermediate score and 42 (40%) cases showed low score. The 3 groups differs significantly with pT (0.027), pN (0.035) and LVI (0.015). Conclusion: The present study showed combining different morphological parameters of tumour and tumour environment can help to further subdivide CRC into prognostically significant subgroups.

Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis.

Tumor budding (TB) is an important prognostic factor in colorectal carcinoma (CRC). Osteopontin (OPN) functions in various processes such as immune response, migration and invasion, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis. However, the involvement of OPN and CD44v6, which is a receptor for OPN, in TB has not been clarified. Therefore, we examined the relationship of OPN with TB in CRC and compared the clinicopathological features. We investigated the expression of OPN and CD44v6 in 83 cases of CRC by immunostaining and analyzed the clinicopathological features. OPN expression was observed mostly in the cytoplasm of stromal cells such as macrophages and fibroblasts, and rarely in cancer cells. There was a significant correlation between OPN positivity and the degree of differentiation at the invasive front and TB grade. CD44v6 was positive in cancer cells in 72 cases (86.7 %) and negative in 11 cases (13.3 %). A statistically significant effect on overall survival (OS) was identified between the OPN-positive group [median OS: 1586 (range, 30-2749) days] and the OPN-negative group [median OS: 1901 (range, 8-2665) days] (log-rank test, p=0.011). OPN analysis in CRC stromal cells may have prognostic implications.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Molecular Basis of Extramural Vascular Invasion (EMVI) in Colorectal Carcinoma

Extramural vascular invasion (EMVI) is a known poor prognostic factor in colorectal carcinoma; however, its molecular basis has not been defined. This study aimed to assess the expression of molecular markers in EMVI positive colorectal carcinoma to understand their tumor microenvironment. Immunohistochemistry was performed on tissue microarrays of surgically resected colorectal cancer specimens for immunological markers, and BRAFV600E mutation (and on the tissue blocks for mismatch repair proteins). Automated quantification was used for CD8, LAG3, FOXP3, PU1, and CD163, and manual quantification was used for PDL1, HLA I markers (beta-2 microglobulin, HC10), and HLA II. The Wilcoxon rank-sum test was used to compare EMVI positive and negative tumors. A logistic regression model was fitted to assess the predictive effect of biomarkers on EMVI. There were 340 EMVI positive and 678 EMVI negative chemo naïve tumors. PDL1 was barely expressed on tumor cells (median 0) in the entire cohort. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 cells, PDL1 positive macrophages, and beta-2 microglobulin on tumor cells in the EMVI positive subset (p ≤ 0.001). There was no association of BRAFV600E or deficient mismatch repair proteins (dMMR) with EMVI. PU1 (OR 0.8, 0.7-0.9) and low PDL1 (OR 1.6, 1.1-2.3) independently predicted EMVI on multivariate logistic regression among all biomarkers examined. There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

Linear Skeletal Muscle Index and Muscle Attenuation May Be New Prognostic Factors in Colorectal Carcinoma Treated by Radical Resection.

ObjectiveThis study evaluated the association between body composition and clinical parameters and prognosis in patients with colorectal cancer (CRC) treated by radical resection.MethodsBaseline data on patient age, body mass index (BMI), bowel obstruction and tumor-related factors were collected retrospectively. Body composition parameters such as visceral fat area (VFA), total abdominal muscle area (TAMA), muscle attenuation (MA), posterior renal fat thickness (PPNF) and intermuscular fat area (IMF) are measured using Computed tomography (CT) scans. We also propose a new predictor of linear skeletal muscle index (LSMI) that can be easily measured clinically at CT. Follow-up endpoints were disease-free survival and all-cause death. We follow up with patients in hospital or by telephone. Univariate and multifactorial Cox proportional hazards analyses were performed to identify risk factors associated with prognosis. Survival analysis was performed using the Kaplan-Meier method and a nomogram was established to predict survival.ResultsA total of 1761 patients (median age 62 years) with CRC were enrolled in our study, of whom 201 had intestinal obstruction and 673 had a BMI > 24.0. Among all patients, the 3- and 5-year disease-free survival rates were 84.55% and 68.60% respectively, and the overall survival rates were 88.87% and 76.38%. Overall survival was significantly correlated with MA, LSMI, SMI, Tumor size, N stage, metastasis and adjuvant therapy by Cox regression analysis (p < 0.05). The risk of tumor progression was significantly associated with MA, VFA, LSMI, SMI, Male, N stage, metastasis and adjuvant therapy (p < 0.05). In addition, based on the Chinese population, we found that female patients with MA < 30.0 HU, LSMI < 18.2, and SMI < 38.0 had a worse prognosis, male patients with MA < 37.6 HU, LSMI < 21.9, and SMI < 40.3 had a poorer prognosis.ConclusionOur findings suggest that linear skeletal muscle index and MA can be used as new independent predictors for colorectal cancer patients treated with radical surgery, and that baseline data such as body composition parameters, LSMI and tumor-related factors can collectively predict patient prognosis. These results could help us to optimize the management and treatment of patients after surgery.

Evaluation of the significance of human class I homeobox A13 and STK4/MST1 expression in conventional colorectal adenoma and adenocarcinoma and correlation with clinicopathological parameters (immunohistochemical study)

Background Colorectal carcinoma (CRC) is the third most common cancer in the world. Human class I homeobox A13 (HOXA13) was initially identified as a transcription factor and has an important role in embryonic development and malignant transformation. Mammalian STE20-like kinase 1 (STK4/MST1) encodes a serine/threonine kinase that is the mammalian homolog of the Hippo pathway and plays an important role in controlling cell growth, apoptosis, and organ size. Aim This work aimed to evaluate the role of HOXA13 and STK4/MST1 in conventional colorectal adenoma and adenocarcinoma. Materials and methods This retrospective study was carried out on 20 cases of conventional colorectal adenoma and 30 cases of conventional colorectal adenocarcinoma. HOXA13 and STK4/MST1 immunostaining was done and assessed for each case. Correlation with the clinicopathological findings and statistical analysis was studied. Results In the carcinoma cases, there was a highly significant direct statistical correlation between HOXA13 expression and tumor grade, lymph node metastasis, and TNM stage (P<0.01 for each). Inverse statistical correlation between STK4/MST1 expression and tumor grade, depth of tumor invasion (T), and TNM stage (P<0.01 for each) was found. HOXA13 and STK4/MST1 immunoexpression showed direct highly significant relation with the transition from adenoma to adenoma with dysplasia to adenocarcinoma (P<0.01). There was a highly significant inverse statistical correlation between HOXA13 and STK4/MST1 expression in the studied cases of CRC (P<0.01). According to receiver-operating characteristic curve, both markers were good in the prediction of metastatic potential in the carcinoma cases using the TNM stage as a parameter with a sensitivity of 85%. Conclusion HOXA13 was immunohistochemically overexpressed, while STK4/MST1 was downexpressed in progression from colorectal adenoma to adenoma with dysplasia to adenocarcinoma cases. HOXA13 and STK4/MST1 might have a potential role as independent prognostic factors in CRC and may have validity to predict metastatic potential of CRC.

Clinicopathologic correlates of tumor deposits, lymph node harvest, lymph node metastasis, and lymph node ratio in colorectal cancer: The importance of mucinous tumor histology

Introduction: The presence of tumor deposits (TDs), number of harvested lymph nodes (LNs), LN metastasis, and LN ratio (LNR) are well-known prognostic factors in colorectal carcinoma. Materials and methods: The relationship between clinicopathologic parameters and the presence of TDs, number of harvested LNs, LN metastasis, and LNR was investigated in 278 consecutive patients who underwent surgery for colorectal adenocarcinoma. Results: Multivariate logistic regression analysis revealed that mucinous tumor histology and lymphovascular invasion (LVI) were independent risk factors for the presence of TD (p=0.016 and p=0.003, respectively). Age, tumor localization, and pT stage were statistically significant parameters affecting harvested LN number (p=0.002, p=0.007, and p=0.028, respectively). Only LVI was an independent risk factor for LN metastasis (p=0.001), whereas advanced age, mucinous tumor histology, and LVI were independent risk factors for higher LNR (p=0.033, p=0.042, and p=0.001, respectively). Conclusions: Our results revealed that mucinous tumor histology was an independent risk factor for the presence of TDs and higher LNR. In addition, LVI - which is a well-known prognostic factor- was also an independent risk factor for the presence of TD and higher LNR. Older age was found to be an independent risk factor for higher LNR. We found that the number of harvested lymph nodes was increased when the patients were younger, the tumor was located on the right colon, and the pT stage was advanced. These results have to be proven in larger cohorts with follow-up data. Keywords: colorectal cancer; mucinous tumor histology; tumor deposit; lymph node ratio; lymph node metastasis.

Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma?

INTRODUCTION:Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC.METHODS:In this retrospective multicentre study, 5,931 LNs from 342 stage I–III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry.Results:One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001).Discussion:The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual , Supplementary Digital Content 2, http://links.lww.com/CTG/A512).

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.

Diagnosis and prognostic significance of extramural venous invasion in neuroendocrine tumors of the small intestine

Extramural venous invasion (EMVI) is an established independent prognostic factor in colorectal carcinoma where it is linked to hematogenous spread (i.e., liver metastases), influencing the decision for adjuvant chemotherapy. However, its prognostic significance in small intestinal neuroendocrine tumors (NETs) has not been studied, nor is it routinely assessed or reported. We reviewed primary small bowel NETs (14 jejunum, 82 ileum, 8 not specified) from 104 patients (52 women; median age 60.5, range: 24–84). EMVI was identified in 58 cases (55.8%), including in 13 of 21 equivocal cases using an elastin stain. In univariate analysis, EMVI was associated with lymphovascular and perineural invasion, tumor stage, and lymph node and distant metastases, whereas in multivariate analysis, only distant metastases remained significant (p < 0.001). Liver metastases were present in 55 cases (52.9%) and were significantly associated in univariate analysis with lymphovascular and perineural invasion, tumor stage, lymph node metastases, and EMVI, whereas in multivariate analysis, only EMVI remained significant (p < 0.001; odds ratio (OR) = 59.42). Eight patients developed metachronous liver metastases during follow-up (mean 22.9 ± 22.0 months, range: 4.7–73.2) and all (100%) were positive for EMVI. In contrast, of 49 patients who never developed liver metastases over significantly longer follow-up (mean 71.0 ± 32.4 months, range: 6.6–150.4; p < 0.001), only 7 (14.3%) had EMVI (p < 0.001). In Kaplan–Meier analysis, 8 of 15 patients with EMVI (53.3%) developed metachronous liver metastases, compared with 0 of 42 patients without EMVI (p < 0.001). In contrast, nonhepatic distant metastases, seen in 26 (25.0%) patients, were not associated with EMVI in multivariate or Kaplan–Meier analyses. Our data demonstrate that EMVI is common in small bowel NETs and strongly correlates with development of liver metastases. Therefore, its evaluation is critical and should be assessed in combination with adjuvant techniques such as elastin staining, if necessary. Moreover, inclusion of EMVI in pathology reporting guidelines should be considered.

Tumor budding in cervical carcinoma: Associations with some clinical and pathological factors

Background: Tumor budding is recognized as an important independent prognostic factor in colorectal carcinoma. The aim of this study was to evaluate the grade of tumor budding and association with other clinical and pathological features in patients with cervical carcinoma. Material and methods: We evaluated pathohistological data from 91 cervical carcinoma patients (mean age: 53.8 years) who underwent radical hysterectomy and pelvic lymphatic dissection at the Oncology Institute of Vojvodina between January 2010 and December 2018. Tumor budding was evaluated in invasive front of the tumor. Based on the number of bud counts/10 high power field, three groups were formed: with no budding, with less than 15 buds, and with more than 15 buds. Results: Eighty (87.91%) of evaluated cervical carcinomas were squamous-cell type, while 12.09% were adenocarcinomas. All carcinomas were graded (HG1-HG3). Average diameter of the tumors was 25 mm (81.6% &lt; 4 cm and 18.4% &gt; 4 cm). Metastases in lymph nodes were present in 30 (32.9%) cases. Based on the number of bud counts/10 high power field there were 35.1% with no budding, 32.9% with less than 15 buds and 37.3% with more than 15 buds. There was a significant association between tumor budding grade and histological grade (p=0.04), as well as with tumor budding grade and the diameter of the tumor (p=0.04). Conclusion: As a quantitative measure of cancer cell dissociation, tumor budding is associated with poor prognosis in cervical carcinoma and should be considered as a prognostic factor.

Immature Stroma and Prognostic Profiling in Colorectal Carcinoma: Development and Validation of Novel Classification Systems

Many pathological characteristics have utility for predicting prognosis in colorectal carcinoma (CRC). Some of the most important include tumor stage (TS), lymph node status (LNS) and tumor budding (TB). Tumor budding is a phenomenon originally described in 1949 as sprouting. TB assessment is not always reliable however, as it is subject to high inter-observer variation. This finding persists despite the current trends for sub-specialty training in surgical pathology. In light of this, new and reproducible histological prognostic markers could change the way we diagnose and manage patients with colorectal carcinoma. Studies have shown that desmoplastic reaction (DR) categorization can actually outperform other conventional prognostic factors, including tumor budding and tumor stage in predicting disease-free survival (DFS). Our study aimed to evaluate and assess the prognostic value of desmoplastic reaction in an American cohort with colorectal cancer using 3 different stromal classification scoring systems. In all three stromal grading systems, immature stroma was the most significant independent prognostic factor in CRC. Currently, none of the reporting protocols for the College of American Pathologists, the Royal College of Pathologists of the United Kingdom, and the Japanese Society for Cancer report on the presence of immature stroma. Importantly, regarding the ability to predict survival outcomes, our novel classification system has the potential to outperform other scoring methodologies.

Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Budding, tumor-infiltrating lymphocytes, gland formation: scoring leads to new prognostic groups in World Health Organization low-grade colorectal cancer with impact on survival

Grading for colorectal carcinoma (CRC) is traditionally based on the percentage of gland formation. In recent years, high-grade CRC has become subject to more precise molecular grading strategies. Most, however, are low-grade cases according to the World Health Organization (WHO) with inhomogenous outcomes due to still insufficient characterization. On the other hand, budding and tumor-infiltrating lymphocytes have developed as interesting additive prognostic factors in CRC. Especially budding has been very well defined by the International Tumor Budding Consensus Conference recently. We analyzed a large collective of 576 WHO low-grade CRC cases, stages I to IV, diagnosed between 2005 and 2016 in terms of gland formation, budding, and tumor-infiltrating lymphocytes and developed a new, morphology-based risk score, taking into account each of the 3 parameters. For each parameter, 1 to 2 points were given, resulting in a sum score, dividing the CRC cases into a low-, an intermediate-, and a high-risk group. By our score, 179 (34.9%) of the cases were grouped as low risk, 241 (53.5) as intermediate risk, and 92 (35.5%) as high risk. The 3 groups differed significantly in pT, pN, and M as well as tumor stages, lymphatic vessel invasion, venous invasion, and overall survival (0.;P < .001 for low risk versus high risk, P = .038 for low versus intermediate risk, and P = .036 for intermediate versus high risk; log rank: median, 94.0 months [95% confidence interval {CI}, 74.9-113.1] for low risk; median, 63.0 months [95% CI, 44.0-82.0] for intermediate risk; and median, 40.0 months [95% CI, 23.4-56.7] for high risk) in Kaplan-Meier-analysis. Our proposed Bayreuth score enables separating the large group of WHO low-grade CRC cases into subgroups, which differ significantly in outcome.

Expression of beta-human chorionic gonadotropin as a prognostic factor in colorectal carcinoma

Background: Colorectal carcinoma (CRC) is a common malignancy in Iraq and carries a high mortality rate. It has been shown that CRCs express high level of beta-human chorionic gonadotropin (β-HCG) as detected by immunohistochemistry. Objectives: The aim of this study was to assess the expression of β-HCG in CRC and to study the association between β-HCG expression and pathological prognostic parameters. Materials and Methods: This study was carried out on 35 colonic specimens consisting of 30 CRC selected from files of Pathologic Laboratory of Al-Kadhymia Teaching Hospital and Teaching Laboratories of the Medical City, Baghdad. Paraffin blocks were cut sections stained with H and E stain and sections for streptavidin-biotin immunohistochemical staining using monoclonal antibody against β-HCG. Immunohistochemical sections were examined for positive or negative staining and positivity assessed as: occasional, focal, and diffuse tumors. Results: Of the 30 CRCs, 60% were male and 40% were female. The most common site of large bowel malignancy was the rectum 13 (43.3%). Most of the tumors were moderately-differentiated adenocarcinoma (83.3%). More than half of the cases were Stage T3, followed by Stage T2, then Stage T4, 3 cases (10%), and no case in Stage T1. Lymph node metastases were found in 19 cases (63.3%). Twelve cases (40%) of CRC show immunoreactivity to β-HCG. β-HCG expression was more frequent in the left side of the large bowel and more common in poorly-differentiated adenocarcinoma (80%). β-HCG was more positive in Stage T4, and there was significant association with lymph node metastasis. Conclusion: Expression of β-HCG in CRC is not an infrequent phenomenon, and no stain was demonstrated in benign and normal colonic specimens, while β-HCG expression associated with poor differentiation, greater local invasion, and regional lymph node metastasis.

Tumour budding : an emerging prognostic factor in colorectal carcinoma

Tumour budding, is a morphological feature seen in colorectal carcinoma and known to be associated with a poor outcome. It is thought to be representing the phenomenon of epithelial-mesenchymal transition of colorectal carcinoma. Colorectal malignancies exhibiting budding have shown an association with lymphatic invasion and lymph node metastasis. In addition, tumour budding has proven to be associated with tumour recurrence and is a negative prognostic indicator of overall survival of patients with colorectal carcinoma. Objectives of the study was to assess the prevalence of tumour budding in CRC (higher colorectal carcinoma) specimens and to determine the association between tumour budding and the histological grade, nodal involvement and tumour recurrence. A retrospective study was carried out at the Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura. The study sample included 58 cases of colorectal carcinoma during the period January 2015 to June 2018. The histological grade, nodal status and tumour recurrence was recorded following review of histology slides. In addition, the slides were examined for the presence or absence of tumour budding, according to the ITBCC (November 2016) recommendations. Study population showed a tumour budding percentage of 32.75%. Tumour budding in colorectal carcinoma showed a statistically significant association with high histological grade, lymph nodal involvement and tumour recurrence (p-value Tumour budding in CRC is strongly predictive of high histological grade, lymph node metastases, and tumour recurrence. The study population included 02 cases of tumour recurrence in the budding group and a single case of cancer-related deaths.

Tumor Budding in Colorectal Carcinoma: Translating a Morphologic Score Into Clinically Meaningful Results.

- Tumor budding has received increasing recognition as an important independent prognostic factor in colorectal carcinoma. Prominent tumor budding in adenocarcinoma arising in a polyp has been shown to be a risk factor for lymph node involvement. The variability in methods used for evaluating tumor budding in different studies and lack of standardized guidelines have impeded routine inclusion of tumor budding in pathology reports. This changed last year with consensus guidelines based on the International Tumor Budding Consensus Conference (ITBCC). These guidelines have been included in the recent College of American Pathologists (CAPs) Colorectal Cancer Protocol. The consensus methodology will allow uniform reporting of this finding, but challenges in interpretation in the setting of intense inflammation, fibrosis, or gland fragmentation need to be addressed in future guidelines. - To provide a brief overview of the known clinical significance of tumor budding in colorectal carcinoma and discuss the practical aspects of its implementation on a routine basis. - English-language pathology literature. - Tumor budding has been shown to be an independent prognostic marker in colorectal carcinomas and the routine reporting of tumor buds is now advocated by using the approach outlined by the ITBCC guidelines. Tumor budding is included in the CAP protocol as a recommended element. Presence of prominent tumor budding in an adenocarcinoma in a polyp may have implications for management, such as additional resection, while it serves as a prognostic factor in other settings.

Expression of Aldehyde Dehydrogenase 1A1 (ALDH1A1) as a Prognostic Biomarker in Colorectal Cancer Using Immunohistochemistry.

BackgroundThe expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is increased in several human tumors, including colorectal carcinoma (CRC). The aim of this study was to compare the expression ALDH1A1 in CRC tumor tissue compared with non-tumor adjacent tissue (NAT), using immunohistochemistry (IHC), and to determine whether the expression of the ALDH1A1 protein was associated with prognostic factors in CRC.Material/MethodsFormalin-fixed paraffin-embedded (FFPE) tissue from 424 patients diagnosed with CRC, and 196 matched NATs were used to prepare tissue microarrays (TMAs). IHC was performed using an immunoperoxidase method with a primary polyclonal rabbit anti-ALDH1A1 antibody. The IHC scores by light microscopy were the staining intensity (scored from 0–3) multiplied by the percentage area of positive immunostaining within the visual field (scored from 0–4). Associations between tumor expression levels of ALDH1A1 and patient clinicopathological characteristics, including tumor grade, size, and TNM stage at surgery were analyzed.ResultsALDH1A1 protein expression was significantly increased in CRC tissues compared with matched NATs. In patients with CRC, increased expression of the ALDH1A1 protein was significantly associated with the presence of lymph node metastasis: 64.28% in N0 cases; 75.49% in N1 cases; and 82.14% in N2 cases, (P=0.002). Univariate and multivariate analysis showed that ALDH1A1 expression was an independent prognostic marker for CRC (P<0.001).ConclusionsUsing IHC, the expression of the ALDH1A1 protein in CRC tissues was significantly associated with the presence of lymph node metastases and might be a potential prognostic marker in patients with CRC.