Prognostic role of the log odds of positive lymph nodes in Western patients with resected gastric cancer: A comparison with the 8th edition of the TNM staging system.

OBJECTIVES: Several alternative lymph node staging systems have recently been described for gastric cancer. The log odds of positive lymph nodes (LODDS) system may be superior to the pN stage (American Joint Committee on Cancer) and lymph node ratio systems in predicting outcomes for patients with gastric cancers, as indicated by some researchers. Most studies, however, have been conducted in Asian countries, and conflicting results have been reported by other investigators. METHODS: We conducted a retrospective study of all 377 cases of gastric cancer resected at a tertiary hospital in Spain between 2000 and 2019. Clinicopathologic features were collected, LODDS were calculated and categorized into 5 groups (S1-S5), and statistical analysis was performed. RESULTS: The cases included (n = 315) were classified as S1 (25.6%), S2 (18.4%), S3 (21.3%), S4 (20.3%), and S5 (14.4%). The LODDS classification was significantly associated with tumor size, Laurén subtype, presence of signet ring cells, tumor grade, perineural infiltration, lymphovascular invasion, growth pattern, pT, tumor recurrence, and death. Kaplan-Meier analysis based on the LODDS classification demonstrated improved patient stratification compared with the pN stage for both overall survival (OS) and disease-free survival (DFS). Area under the curve values for recurrence and death were superior for the LODDS classification, and this classification was independently related to OS and DFS. In addition, the LODDS classification successfully divided patients without lymph node metastases (pN0) into subgroups with distinct prognoses. CONCLUSIONS: For our cohort, the LODDS system showed better prognostic performance than pN stage; it was an independent predictor of OS and DFS, and it provided valuable prognostic information in cases without lymph node metastases. Its prognostic accuracy, however, decreased in cases with fewer than 16 lymph nodes resected.

Prognostic role of the number of resected and negative lymph nodes in Spanish patients with gastric cancer.

INTRODUCTION: Lymph node (LN) involvement is one of the most critical prognostic factors in resected gastric cancer (GC). Some analyses, mainly conducted in Asian populations, have found that patients with a higher number of total lymph nodes (NTLN) and/or negative lymph nodes (NNLN) have a better prognosis, although other authors have failed to confirm these results. MATERIALS AND METHODS: Retrospective study including all patients with GC resected in a tertiary hospital in Spain between 2001 and 2019 (n = 315). Clinicopathological features were collected and patients were categorized according to the NTLN and the NNLN. Statistical analyses were performed. RESULTS: Mean NNLN was 17. The NNLN was significantly related to multiple clinicopathological variables, including recurrence and tumor-related death. The classification based on the NNLN (N1: ≥16, N2: 8-15, N3: ≤7) effectively stratified the entire cohort into three distinct prognostic groups and maintained its prognostic value within both the pN0 and pN+ patient subsets. Furthermore, it was an independent prognostic indicator for both overall and disease-free survival. Conversely, the mean NTLN was 21.9. Patients with ≤16 LN retrieved exhibited distinct clinicopathological features compared to those with >16 LN, but no significant differences were observed in terms of recurrence or disease-associated death. The application of alternative cut-off points for NTLN (10, 20, 25, 30, and 40) showed no prognostic significance. CONCLUSIONS: In Spanish patients with resected GC the NNLN hold prognostic significance, while the NTLN does not appear to be prognostically significant. Incorporating the NNLN into GC staging may enhance the accuracy of the TNM system.

Impact of Age at Diagnosis on Clinicopathological Features, Prognosis, and Management of Gastric Cancer: A Retrospective Single-Center Experience from Spain.

The impact of age on various aspects of gastric cancer (GC) remains controversial. Clarifying this issue can improve our understanding of the disease, refine risk stratification models, and aid in personalized therapeutic approaches. This study aimed to evaluate the influence of age at diagnosis on the clinicopathological features, prognosis, and management of a specific cohort of Spanish patients with resected GC. The study encompassed 315 patients treated at a single tertiary hospital in Spain, divided into two age-based subgroups: ≤65 years and >65 years. The mean and median ages at diagnosis were 72 and 76 years. Most tumors were diagnosed at pT3 stage (49.2%), and 59.6% of patients had lymph node metastases. 21.3% of cases were diagnosed with GC at age ≤ 65 years. Younger patients showed a significantly higher prevalence of flat, diffuse, high-grade tumors, signet-ring cells, perineural infiltration, D2 lymphadenectomies, and adjuvant therapy. They also exhibited a higher rate of recurrences, but had a significantly longer follow-up. Kaplan-Meier curves indicated no significant prognostic differences based on age. Finally, age did not independently predict overall survival or disease-free survival. Our results suggest that younger patients may require more aggressive treatment due to adverse clinicopathologic features, but the lack of prognostic differences among age groups in our cohort indicates the need for further investigation into the complex interplay between age, clinicopathologic factors, and long-term outcomes in GC.

Clinicopathological differences, risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer.

BACKGROUND: In the molecular era, the Laurén system is still a cost-effective and widely implemented classification for gastric cancer (GC) and it has been recently associated with clinical, histological and molecular features of these tumors. Despite recent advances in the understanding of the molecular biology of GC, there is a need to develop new prognostic tools for patient stratification in clinical practice. Thus, the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC. AIM: To identify clinicopathological differences, risk factors, and to develop cost-effective prognostic scores for patients with intestinal and diffuse-type GC. METHODS: Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019. 286 cases met inclusion criteria (intestinal: 190, diffuse: 96). Clinical data and gross findings were collected. All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed. Five tissue microarrays (TMAs) were constructed and sections of the TMA block were immunostained for HERCEPTEST, MSH2, MSH6, MLH1 and PMS2. Statistical analyses were performed and prognostic scores were developed based on hazard ratios. RESULTS: Intestinal and diffuse-type GC showed different epidemiological, clinicopathological and prognostic features. Diffuse tumors were significantly associated with younger age, less symptomatology, flat morphology, deeper invasion, perineural infiltration, advanced stage at diagnosis, administration of adjuvant therapy and poorer prognosis. Intestinal lesions were fungoid or polypoid, showed necrosis, desmoplasia, microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages. Tumor depth, desmoplasia, macroscopic type and lymph node involvement were independently related to the Laurén subtype. Furthermore, intestinal and diffuse GC were associated with different risk factors for progression and death. Vascular invasion, perineural infiltration and growth pattern were important prognostic factors in intestinal-type GC. On the contrary, tumor size and necrosis were significant prognosticators in diffuse-type GC. Our recurrence and cancer-specific death scores for patients with intestinal and diffuse-type GC showed an excellent patient stratification into three (diffuse GC) or four (intestinal) prognostic groups. CONCLUSION: Our findings support that Laurén subtypes represent different clinicopathological and biological entities. The development of specific prognostic scores is a useful and cost-effective strategy to improve risk assessment in GC.

Pathologic Lymph Node Staging of Gastric Cancer.

OBJECTIVES: The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC. METHODS: Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC. RESULTS: Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC. CONCLUSIONS: Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Are Borrmann's Types of Advanced Gastric Cancer Distinct Clinicopathological and Molecular Entities? A Western Study.

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC.

Towards standardization of lymph-node ratio classifications: Validation and comparison of different lymph node ratio classifications for predicting prognosis of patients with resected gastric cancer.

INTRODUCTION: The TNM staging system is the main prognostic tool for GC, but the number of metastatic lymph nodes (LN) can be affected by surgical, pathological, tumor or host factors. Several authors have shown that lymph node ratio (LNR) may be superior to TNM staging in GC. However, cut-off values vary between studies and LNR assessment is not standardized. MATERIAL AND METHODS: Retrospective study of all GC resected in a western tertiary center (N = 377). Clinical features were collected and pathological features were assessed by two independent pathologists. Eight LNR classifications were selected and applied to our patients. Statistical analyses were performed. RESULTS: 315 patients were included. Most tumors were T3 (49.2%) N+ (59.3%). During follow-up, 36.7% of patients progressed and 27.4% died due to tumor. All LNR classifications were significantly associated with clinicopathological features such as Laurén subtype, lymphovascular invasion, perineural infiltration, T stage, tumor progression or death. All LNR classifications were independent prognostic factors for OS and DFS, and ROC analyses calculated similar AUC values for all staging systems. Kaplan-Meier curves showed that Pedrazzani, Wang, Liu and Huang classifications stratified patients better into three (Pedrazzani) or four categories. These classifications tended to downstage TNM N2 and N3 tumors. In cases with less than 16 LNs resected, Pedrazzani and Wang classifications showed the best prognostic performance. CONCLUSIONS: Pedrazzani, Wang, Liu and Huang classifications showed good prognostic performance in western GC patients. Larger studies in other cohorts are needed to identify the most consistent LNR classification for GC.

Is there still a place for conventional histopathology in the age of molecular medicine? Laurén classification, inflammatory infiltration and other current topics in gastric cancer diagnosis and prognosis.

Gastric cancer (GC) is the fifth most common cancer and the third cause of cancer-related deaths worldwide. In western countries, more than half of GC patients are diagnosed at advanced stages and 5-year survival rates range between 20-30%. The only curative treatment is surgery, and despite recent advances in oncological therapies, GC prognosis is still poor. The main prognostic tool for patient categorization and treatment selection is the TNM classification, but its limitations are being increasingly recognized. Early recurrences may occur in early-stage disease, and patients at the same stage show heterogeneous outcomes. Thus, there is a need to improve GC stratification and to identify new prognostic factors, which may allow us to select drug-susceptible populations, refine patient grouping for clinical trials and discover new therapeutic targets. Molecular classifications have been developed, but they have not been translated to the clinical practice. On the other hand, histological assessment is cheap and widely available, and it is still a mainstay in the era of molecular medicine. Furthermore, histological features are acquiring new roles as reflectors of the genotype-phenotype correlation, and their potential impact on patient management is currently being analyzed. The aim of this literature review is to provide a modern overview of the histological assessment of GC. In this study, we discuss recent topics on the histological diagnosis of GC, focusing on the current role of Laurén classification and the potential value of new histological features in GC, such as inflammatory infiltration and tumor budding.

Development of a simplified tumor-lymph node ratio classification system for patients with resected gastric cancer: A western study.

INTRODUCTION: Gastric cancer (GC) shows high recurrence and mortality rates. The AJCC TNM staging system is the best prognostic predictor, but lymph node assessment is a major source of controversy. Recent studies have found that lymph node ratio (LNR) may overcome TNM limitations. Our aim is to develop a simplified tumor-LNR (T-LNR) classification for predicting prognosis of resected GC. METHODS: Retrospective study of all GC resected in a tertiary center in Spain (N = 377). Clinicopathological features were assessed, LNR was classified into N0:0%, N1:1-25%, N2:>25%, and a T-LNR classification was developed. Statistical analyses were performed. RESULTS: 317 patients were finally included. Most patients were male (54.6%) and mean age was 72 years. Tumors were intestinal (61%), diffuse (30.8%) or mixed (8.1%). During follow-up, 36.7% and 27.4% of patients progressed and died, respectively. T-LNR classification divided patients into five prognostic categories (S1-S5). Most cases were S1-S4 (26.2%, 19.9%, 22.6% and 23.6%, respectively). 7.6% of tumors were S5. T-LNR classification was significantly associated with tumor size, depth, macroscopical type, Laurén subtype, signet ring cells, histologic grade, lymphovascular invasion, perineural infiltration, infiltrative growth, patient progression and death. Kaplan-Meier curves for OS showed an excellent patient stratification with evenly spaced curves. As for DFS, T-LNR classification also showed good discriminatory ability with non-overlapping curves. T-LNR classification was independently related to both OS and DFS. CONCLUSIONS: T-LNR classifications can successfully predict prognosis of GC patients. Larger studies in other geographic regions should be performed to refine this classification and to validate its prognostic relevance.

Proposal for a clinicopathological prognostic score for resected gastric cancer patients.

BACKGROUND: Factors other than pTNM stage have been associated with gastric cancer (GC) prognosis, and several alternative prognostic scores have been constructed. Our aims are to identify prognostic factors in western GC patients and to build clinicopathological prognostic models for overall survival (OS) and disease-free survival (DFS). METHODS: A Retrospective study of 204 cases of GC resected during the years 2000 to 2014 was conducted in our hospital. Clinicopathological features were assessed, univariate and multivariate analysis were performed and prognostic scores were constructed. RESULTS: Most patients were diagnosed at pTNM stages II and III (36.9% and 48.1%, respectively). According to Laurén classification, tumors were intestinal (55.8%), diffuse (35.2%) and mixed (9%). During follow-up, 43.5% of patients had tumor recurrence, and 28.6% died due to tumor. Univariate analysis showed that patient age, Laurén subtype, signet-ring cell morphology, pTNM stage, tumor grade, perineural invasion, growth pattern, intratumoral inflammation, adjuvant therapy, and desmoplasia were significantly related to tumor progression or death. Multivariate analysis showed that Laurén subtype, pT stage, and lymph node ratio (LNR) were significantly and independently associated with GC recurrence. Laurén subtype and LNR were significantly related to patient survival. Prognostic scores for tumor progression and death were developed and patients were classified into four prognostic groups which showed good prognostic performance. CONCLUSION: A prognostic model comprising histological features such as Laurén subtype can be easily applied in clinical practice, and provides more prognostic information than pTNM stage alone. These models can further stratify resected GC patients and have the potential to aid in the individualization of patient management.

Which Lymph Node Staging System Better Predicts Prognosis in Patients With Gastric Carcinoma? A Comparative Study Between 3 Different Lymph Node Classifications for Resected Gastric Cancer in a Western Tertiary Center.

INTRODUCTION: Gastric cancer (GC) is an aggressive disease with high mortality rates. Lymph node (LN) staging of GC is a major source of controversy. The aim of this study is to compare the prognostic value of 3 different LN classifications for patients with resected GC: the eighth TNM staging system, lymph node ratio (LNR, ratio between positive and total LN) and a new anatomic-based classification (Choi classification). MATERIALS AND METHODS: A retrospective study of all cases of GC resected in a tertiary hospital in Spain (n=377). Clinical data were collected; histologic slides were reviewed; and univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed. RESULTS: In all, 315 patients fulfilled inclusion criteria. Univariate analysis showed that all classifications were significantly associated with tumor death and progression (P<0.001). All staging systems were independent prognostic factors for DFS. Area under the curve ratios for Choi, N stage, and LNR classifications were 0.738, 0.730, and 0.735, respectively. TNM and LNR classifications were independent prognosticators for OS, while Choi classification was an independent factor only in patients with ≥16 LN resected. Area under the curve ratios for Choi, N stage, and LNR classifications were 0.707, 0.728, and 0.732, respectively. Kaplan-Meier curves depending on LNR classification showed the best patient stratification for both OS and DFS. CONCLUSIONS: The 3-staging systems had similar prognostic performance, but LNR-based classification stratified patients better. Further studies are needed to evaluate the impact of the number of LN examined, cutoff values, and anatomic extent of LN disease in GC.

Update, validation and comparison of three different clinicopathological scores for patients with resected gastric cancer: A western experience.

INTRODUCTION: Gastric cancer (GC) is a multifactorial disease. Several prognostic scores have been proposed for refining the prognostic information provided by the TNM classification. Our aim is to validate and compare the prognostic performance of different clinicopathological scores in a western cohort of patients (Marubini, Haraguchi and Kologlu scores). MATERIAL AND METHODS: Retrospective study of all cases of GC resected in a western tertiary center (N = 377). Clinicopathological features were collected, scores were applied and statistical analyses were performed. RESULTS: 315 cases were finally included. According to Marubini, Haraguchi and Kologlu scores, patients were stage I (18.5%, 13.3% and 49%), II (29.3%, 47.2% and 29.5%) and III (52.2%, 39.5% and 21.5%, respectively). All classifications were significantly associated with lymphovascular invasion, perineural infiltration, lymph node involvement, patient progression and death due to GC. All scores showed good patient stratification by Kaplan-Meier analyses, but OS and DFS curves depending on Haraguchi score were less evenly spaced. Kologlu classification showed prognostic superiority over Haraguchi and Marubini classifications by ROC analysis. AUC values for OS and DFS were 0.654 and 0.647 (Marubini), 0.626 and 0.618 (Haraguchi) and 0.724 and 0.709 (Kologlu). Kologlu and Marubini classifications were independent factors for both OS and DFS, but Haraguchi classification was independently associated only with DFS. CONCLUSIONS: Clinicopathological scores can be easily validated and are cost-effective. Kologlu score is the most thorough classification, and it showed the best prognostic performance for both DFS and OS in our study. More studies are needed to validate its value in other populations.

Prognostic Role of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Immunohistochemical Expression in Patients with Resected Gastric Carcinomas.

Aryl hydrocarbon receptor (AHR) interacting protein (AIP) is a chaperone which binds to inactive AHR in the cell cytoplasm. AHR is best known for mediating the toxicity of halogenated aromatics, but it has also been linked to carcinogenesis and tumor progression in several tumor types. Our aims are to assess the features of AIP immunohistochemical (IHC) staining and to evaluate its possible role as a prognostic marker in gastric cancer (GC). Retrospective study of 147 cases of resected GC. Clinicopathological features were collected, tissue microarrays were constructed for AIP IHC and statistical analysis were performed. AIP staining was observed in 50.3% of tumors. All AIP-positive cases exhibited cytoplasmic or membranous staining, variably associated with nuclear co-staining. 93.2% of AIP-positive tumors showed AIP immunoreactivity in 100% of cells. Staining intensity was mild, moderate and intense in 33.8%, 13.5% and 52.7% of cases. Tumors were stratified according to AIP staining intensity into low expression (no or mild AIP immunoreactivity) and high expression (moderate or intense AIP immunoreactivity). 36.6% of our cases showed high AIP expression. High AIP expression was significantly and independently correlated to tumor progression and cancer death. Tumors with high AIP expression showed lower survival and higher progression rates. AIP expression might be useful for determining GC prognosis. More studies are needed to clarify the role of AHR pathway in GC, AIP expression and its potential use as a surrogate marker for selecting patients for AHR modulation therapy.

Influencia pronóstica de la expresión de CDX2 en carcinoma gástrico operado con intención curativa / Prognostic influence of CDX2 expression in gastric carcinoma after surgery with a curative intent

Introducción y objetivo: el factor de transcripción de la homeocaja relacionada con caudal (CDX2) es un factor de transcripción específico que es importante en la diferenciación temprana, el mantenimiento de la célula epitelial intestinal durante el desarrollo gastrointestinal y como supresor tumoral. El objeto de este estudio es valorar el potencial papel de la expresión de CDX2 como predictor pronóstico. Material y métodos: de los 206 pacientes con carcinoma gástrico sometidos a cirugía con intención curativa, reclutamos a 92 (44,6%), a los que se les realizó tinción inmunohistoquímica con CDX2. El 51,1% son mujeres y la edad promedio fue de 74,07 años. El 56,5% son de tipo intestinal; el 33,7%, de tipo difuso; y el 9,8%, de tipo mixto. El 23,9% son T1/T2 y el 76,1%, T3/T4. Se identificaron metástasis ganglionares (N+) en el 69,6%. El 13% (12) son de estadio clínico I, el 40,2% (37) de II y el 46,7% (43) de III. Resultados: el 68,5% (63) expresó CDX2. Nuestro estudio indica que la expresión de CDX2 (HR 0,339, p = 0,024) representa un indicador de riesgo independiente, junto con el tipo de Lauren (HR 3,471, p = 0,022). Existe asociación entre un menor estadio clínico y la expresión de CDX2 (estadio I) (p = 0,046). Hay una diferencia significativa en términos de supervivencia global para los pacientes con expresión positiva de CDX2 (85,2% vs. 65,5%, p = 0,014). Conclusión: nuestros resultados confirman que la expresión de CDX2 en el carcinoma gástrico indica un mejor pronóstico. Se necesitan más estudios para poder obtener conclusiones definitivas

Introduction and objectives: CDX2 is a specific transcription factor with a significant role in the early differentiation and maintenance of intestinal epithelial cells during gastrointestinal development and also as a tumor suppressor. The aim of this study was to assess the potential role of CDX2 expression as a prognostic predictor. Material and methods: ninety-two of 206 (44.6%) patients with gastric carcinoma that underwent a curative surgery and had immunohistochemical staining for CDX2 were enrolled into the study; 51.1% were female and the average age was 74.07 years. Overall, 56.5% of tumors were of the intestinal type, 33.7% were diffuse and 9.8% were mixed; 23.9% were T1/T2, 76.1% were T3/T4 and lymph node metastases (N+) were identified in 69.6% of cases; 13% (12) were clinical stage I, 40.2% (37) were stage II and 46.7% (43) were stage III. Results: a total of 68.5% (63) expressed CDX2. Our study suggests that CDX2 expression (HR = 0.339, p = 0.024) represents an independent risk marker together with the Lauren type (HR = 3.471, p = 0.022). There was association between a milder clinical stage and CDX2 expression (stage I) (p = 0.046). A significant difference was found in overall survival that favored patients with positive CDX2 expression (85.7% vs 65.5%, p = 0.012). Conclusion: our results confirm that CDX2 expression in gastric carcinoma is associated with improved prognosis, although further studies are needed to draw definitive conclusions

Prognostic influence of CDX2 expression in gastric carcinoma after surgery with a curative intent.

INTRODUCTION AND OBJECTIVES: CDX2 is a specific transcription factor with a significant role in the early differentiation and maintenance of intestinal epithelial cells during gastrointestinal development and also as a tumor suppressor. The aim of this study was to assess the potential role of CDX2 expression as a prognostic predictor. MATERIAL AND METHODS: ninety-two of 206 (44.6%) patients with gastric carcinoma that underwent a curative surgery and had immunohistochemical staining for CDX2 were enrolled into the study; 51.1% were female and the average age was 74.07 years. Overall, 56.5% of tumors were of the intestinal type, 33.7% were diffuse and 9.8% were mixed; 23.9% were T1/T2, 76.1% were T3/T4 and lymph node metastases (N+) were identified in 69.6% of cases; 13% (12) were clinical stage I, 40.2% (37) were stage II and 46.7% (43) were stage III. RESULTS: a total of 68.5% (63) expressed CDX2. Our study suggests that CDX2 expression (HR = 0.339, p = 0.024) represents an independent risk marker together with the Lauren type (HR = 3.471, p = 0.022). There was association between a milder clinical stage and CDX2 expression (stage I) (p = 0.046). A significant difference was found in overall survival that favored patients with positive CDX2 expression (85.7% vs 65.5%, p = 0.012). CONCLUSION: our results confirm that CDX2 expression in gastric carcinoma is associated with improved prognosis, although further studies are needed to draw definitive conclusions.

Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival.

Several classification systems have been described for stratifying patients with gastric carcinoma (GC). However, their prognostic value is low, and there is an urgent need for identification of molecular markers and development of new classifications. Retrospective study of 206 cases of GC diagnosed and surgically resected in our hospital between 2000 and 2017. Clinicopathological features of all cases were assessed and tissue microarrays were constructed for immunohistochemical (IHC) study. Patients were stratified based on IHC results. Mean patient age was 71 years and most patients were male (54.6%). Most tumors were located in the gastric antrum and body, and they were mostly fungoid or ulcerative lesions. GC were mainly intestinal-type tumors and 60.3% were diagnosed at pT3. 56.2% of patients showed recurrences and 29.4% died due to GC. According to our IHC classification, 23.5% of tumors showed microsatellite instability, 6% were E-cadherin negative, 53.5% were stable-p53 not overexpressed, and 17% were stable with p53 overexpression. IHC classification was significantly correlated with patient gender, gross morphology, Laurén classification, tumor necrosis, perineural infiltration, type of leading edge, and patient outcome. Multivariate analysis showed that IHC subtype was significantly and independently associated with overall survival, together with clinical symptoms, signet cell phenotype, tumor grade and vessel invasion. The application of IHC classifications based on molecular biomarkers in clinical practice can aid in the stratification of GC patients. More studies are needed to evaluate the reproducibility and clinical significance of these classifications.

The surface topography of the choroid plexus. Environmental, low and high vacuum scanning electron microscopy.

Environmental scanning electron microscopy (ESEM) allows the examination of hydrated and dried specimens without a conductive metal coating which could be advantageous in the imaging of biological and medical objects. The aim of this study was to assess the performance and benefits of wet-mode and low vacuum ESEM in comparison to high vacuum scanning electron microscopy (SEM) using the choroid plexus of chicken embryos as a model, an organ of the brain involved in the formation of cerebrospinal fluid in vertebrates. Specimens were fixed with or without heavy metals and examined directly or after critical point drying with or without metal coating. For wet mode ESEM freshly excised specimens without any pre-treatment were also examined. Conventional high vacuum SEM revealed the characteristic morphology of the choroid plexus cells at a high resolution and served as reference. With low vacuum ESEM of dried but uncoated samples the structure appeared well preserved but charging was a problem. It could be reduced by a short beam dwell time and averaging of images or by using the backscattered electron detector instead of the gaseous secondary electron detector. However, resolution was lower than with conventional SEM. Wet mode imaging was only possible with tissue that had been stabilized by fixation. Not all surface details (e.g. microvilli) could be visualized and other structures, like the cilia, were deformed. In summary, ESEM is an additional option for the imaging of bio-medical samples but it is problematic with regard to resolution and sample stability during imaging.