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Introduction

Background: Small bowel cancers are rare, accounting for less than 5% of gastrointestinal cancers, but their incidence is increasing. Small bowel adenocarcinoma (SBA) accounts for one-third of small bowel cancers, and due to its rarity, scarce data exist on its molecular and clinicopathological features. The genomic profiling of SBA has been shown to be distinct from colorectal cancer and gastric cancer through comprehensive analysis of genomic alterations. The low incidence of APCmutations in SBA suggests that the adenoma-carcinoma sequence is not the main carcinogenic mechanism. However, the extent to which the Wnt β-catenin signaling pathway, which is important in the adenoma-carcinoma sequence, is involved in the process of carcinogenesis in SBA remains controversial.

Aims & Methods

Aims: We examined the clinicopathological significance of gene mutations involved in the Wnt/β-catenin pathway and their downstream target gene products in SBA.
Methods: Immunostaining for β-catenin, Cyclin D1, c-Myc, E-cadherin and p53 was performed in 69 surgical resections from patients with primary SBA. Genomic alterations were analyzed by targeted next-generation sequencing in 32 cases out of the 69 cases. For cyclin D1 and c-Myc, cases showing nuclear staining in ≥ 10% of cancer cells were considered positive. For E-cadherin and β catenin, cases showing membranous staining equivalent to that of normal small intestinal epithelial cellsin > 75% of cancer cells were considered preserved expression and otherwise considered reduced expression.

Results

Results: Patients included 49 men and 20 women, ranging in age from 32 to 84 years (mean 65 years; median 68 years). At the time of analysis, 21 patients had died. The overall 5-year survival rate was 64%. The median follow-up duration for the entire series was 36 months (mean 51.4 months; range, 5-124 months). The primary localisation of the tumor was the duodenum (n=36), jejunum (n=28), and ileum (n=5). Fifty-fivecases were well differentiated; 9, poorly differentiated; and 5, mucinous adenocarcinoma. In terms of TNM classification, 25cases were stage I; 16, stage II; 12 stage III; and 16, stage IV. Reduced membranous β-catenin staining pattern, which correspond to an activation of the Wnt/β-catenin pathway in cancer cells was observed in 39% of the cases. Cyclin D1 and c-Myc was positive in cancer cells in 58% and 30% of cases, respectively. A significant positive relationship was observed between aberrant β-catenin and cyclin D1. The Wnt pathway-associated gene mutations in SBA were APC in 18.8% and CTNNB1 in 12.5% of the cases, and no cases exhibited both of them. Concurrent reduced β-catenin immunostaining was observed in 4/4 CTNNB1 and 2/6 APC mutation cases, respectively. Reduced β-catenin immunostaining correlated significantly with lymph node metastasis and distant metastasis, and thereby advanced TNM stage. Furthermore, a combined reduced E-cadherin and β-catenin expression was associated with worse prognosis, independent of lymph node metastasis by Cox regression multivariate analysis.

Conclusion

Conclusion: Wnt-related genomic alterations including APCand CTNNB1 were only found in a third of cases examined. The above results suggest that the Wnt/β-catenin pathway is involved in carcinogenesis and cancer progression in SBA, although to a lesser extent than in colorectal cancer.

CLINICOPATHOLOGICAL SIGNIFICANCE OF WNT/Β-CATENIN SIGNALING PATHWAY-RELATED GENES AND PROTEINS IN SPORADIC SMALL BOWEL ADENOCARCINOMA

Ryosuke Inoue 1, Atsushi Tatsuguchi 1, Takeshi Yamada 1, Yuka Shimazu 1, Hanami Machida 1, Ryohei Hamakubo 1, AITOSHI HOSHIMOTO 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Shu Tanaka 1, Shunji Fujimori 1, Katsuhiko Iwakiri 1

1 Nippon Medical School, Tokyo, Japan

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Challenges in upper GI and small bowel cancer (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

The molecular and clinicopathological features of primary small bowel adenocarcinoma (SBA) are less well understood than those of colorectal and gastric cancers, primarily due to its rarity. Cancer stem cells, a small subpopulation of tumor cells, are capable of initiating tumors and contributing to relapse. However, the clinicopathological significance of cancer stem cell marker expression in SBA remains unclear.

Aims & Methods

To investigate the localization and clinicopathological relevance of stem cell markers in SBA, we conducted immunohistochemical analysis of CD44, CD44v, CD44v9, CD133, Lgr5, β-catenin and E-cadherin using formalin-fixed paraffin-embedded tissue samples from 57 SBA cases. DNA mismatch repair (MMR) status was assessed through immunostaining for MLH1, MSH2, MLH6, and PMS2. We then compared the expression patterns with clinicopathological data, including sex, age, localization, histological type, depth of invasion, lymph node metastasis, distant metastasis, clinical stage, disease-free survival and cancer-specific survival. Correlations between protein expression and prognosis were evaluated using the Kaplan-Meier method and Cox proportional hazards regression analysis.

Results

The mean follow-up period was 52 months (median: 46; range: 4–110 months), during which 19 patients died. Tumor localization was as follows: duodenum (n=24), jejunum (n=28), and ileum (n=5). Histologically, 47 tumors were well differentiated, 6 poorly differentiated, and 4 were mucinous adenocarcinoma. According to the TNM classification, 15 cases were stage I, 18 stage II, 10 stage III, and 14 stage IV. Positive expression rates for each protein were CD44, 54%; CD44v6, 46%; CD44v9, 49%; CD133, 39%; and Lgr5, 37%. Lgr5 expression was significantly correlated with lymph node metastasis, distant metastasis, and advanced TNM stage. It was also associated with reduced membranous β-catenin staining, indicative of Wnt/β-catenin pathway activation. CD44 and its variants were significantly associated with both lymph node metastasis and distant metastasis, as well as abnormal reduced membranous β-catenin staining and E-cadherin staining. CD133 was expressed in 39% of cases but did not correlate with any clinicopathological factors. Notably, its expression was higher in MMR-proficient tumors compared to MMR-deficiency ones. Univariate analysis identified histological type, depth of invasion, lymph node metastasis, CD44, CD44v6, CD44v9, CD133 and Lgr5 expression as significantly associated with cancer-specific survival. In multivariate analysis, both lymph node status (hazard ratio: 16.4) and Lgr5 expression (hazard ratio: 3.7) retained independent prognostic significance. For disease-free survival, univariate analysis using the Cox proportional hazards model revealed that lymph node metastasis, CD44v6 and Lgr5 had significant prognostic value. Multivariate analysis confirmed lymph node metastasis (hazard ratio: 31.2) and Lgr5 expression (hazard ratio: 28.7) as independent predictors of poorer disease-free survival.

Conclusion

Our findings suggest that all analyzed cancer stem cell markers had prognostic relevance in SBA. CD44 and its variant isoforms expression are associated with epithelial-mesenchymal transition. Lgr5 expression is linked to Wnt/β-catenin pathway and is an independent predictor of poor cancer-specific survival and disease-free survival, regardless of lymph node metastasis.

CLINICOPATHOLOGICAL SIGNIFICANCE OF CANCER STEM CELL MARKERS IN SMALL BOWEL ADENOCARCINOMA

Atsushi Tatsuguchi 1, Takeshi Yamada 1, Naohiko Akimoto 1, Takayoshi Nishimoto 1, Jun Omori 1, Yuka Shimazu 1, Hanami Machida 1, Ryosuke Inoue 1, Shu Tanaka 1, Shunji Fujimori 1, Masanori Atsukawa 1

1 Nippon Medical School, Tokyo, Japan

Conference

UEG Week Berlin 2025

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Back to the basics of gastric cancer (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

The low incidence of APC gene mutations (less than 30%) in small bowel adenocarcinoma (SBA) suggests that the adenoma-carcinoma-sequence is not the main carcinogenic mechanism. However, the presence or absence of activation of the Wnt/β-catenin signaling pathway, which is important in the adenoma-carcinoma-sequence, has not been sufficiently investigated in SBA. Therefore, we examined gene mutations involved in the Wnt/β-catenin pathway and their downstream target gene products in SBA.

Aims & Methods

We examined 30 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by targeted next-generation sequencing (NGS). DNA mismatch repair (MMR) status was determined by immunostaining for all MMR proteins; MLH1, MSH2, MLH6, and PMS2. In addition, immunostaining for cyclin D1, c-myc, and β-catenin was performed to compare the results of NGS. Nuclear/cytoplasmic or loss of membranous β-catenin staining in cancer cells was defined as aberrant β-catenin immunostaining.

Results

The main genomic alterations found in SBA tumors were TP53 (56.7%), followed by KRAS (33.3%), APC (16.7%), PIK3CA (16.7%), CTNNB1 (10%), BRAF (6.7%), and CDKN2A (6.7%). Deficient MMR tumors were observed in 20% of patients. APC mutations were significantly higher in deficient MMR tumors than in proficient MMR tumors (P=0.041). On the other hands, CTNNB1 mutations were not found in deficient MMR tumors. No cases exhibited both the APC and the CTNNB1 mutations. Aberrant β-catenin immunostaining in cancer cells was observed in 12 out of 30 cases (40%). All three CTNNB1 mutation cases were associated with aberrant β-catenin staining, whereas only 1 of 5 APC mutation cases had aberrant β-catenin staining. The remaining 8 cases with aberrant β-catenin staining had neither APC nor CTNNB1 mutations. Cyclin D1, a representative target protein of the Wnt/β-catenin pathway, was positive in cancer cells in 18 (60%) of the cases. C-myc was positive in cancer cells in 6 (20%) cases. Of the 5 cases with APC mutations, cyclin D1 was positive in two cases and c-myc was positive in one case. Three cases were negative for both cyclinD1 and c-myc, but were associated with MMR deficiency and TP53 mutations. Of the three cases with CTNNB1 mutations, cylclin D1 was positive in two cases and c-myc was positive in one case. All three cases had proficient MMR. Two of the three cases did not have TP53 nor KRAS mutations.

Conclusion

The Wnt pathway-associated gene mutations in SBA were APC and CTNNB1, with one or the other found in 26.7% of cases examined. This frequency is much lower than in colorectal cancer, consistent with previous reports. In addition, 3 out of 5 cases with APC mutations showed normal membranous staining for β-catenin, cyclin D1-negative, and c-myc-negative, suggesting that the Wnt pathway is less activated in these three cases. In addition, these three cases had TP53 mutations and were MMR deficient. This suggests the possibility that APC mutations do not necessarily contribute directly to the carcinogenesis of SBA. On the other hand, the staining abnormality of β-catenin, a key component of the Wnt/β-catenin signaling pathway, suggests that this pathway is activated in half of SBA cases. These results indicate that the Wnt/β-catenin pathway may be activated or deregulated by mechanisms other than APC and CTNNB1 mutations in SBA.

EXPRESSION OF WNT/Β-CATENIN PATHWAY MOLECULES IN SMALL BOWEL ADENOCARCINOMA

Ryosuke Inoue 1, Atsushi Tatsuguchi 1, AITOSHI HOSHIMOTO 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Katsuhiko Iwakiri 1

1 Nippon Medical School Hospital, Tokyo, Japan

Conference

UEG Week Copenhagen 2023

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

PP 03 Small intestinal (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

The molecular and clinicopathological features of primary small bowel adenocarcinoma (SBA) are not as fully understood as are those of colorectal cancer and gastric cancer because SBA is relatively rare. According to the stem cell hypothesis, only a very small number of cancer cells in a tumor have the ability to promote its growth and development. CD44 and CD44 variant isoforms are known as stem cell markers of colorectal cancer. CD44 upregulation has been shown associated with cancer progression, invasion, and metastasis. In addition, CD44 plays an important role in epithelial-mesenchymal transition. However, the clinicopathological significance of CD44 and CD44 isoforms expression in SBA remains unclear.

Aims & Methods

To explore the localisation and clinicopathological significance of CD44 and CD44 variant isoforms in SBA.
We performed immunohistochemical analysis of CD44, CD44v, CD44v9, β-catenin and E-cadherin using formalin-fixed paraffin-embedded tissue specimens obtained from 50 cases of SBA. For E-cadherin and β-catenin, cases showing membranous staining equivalent to that of normal small intestinal epithelial cells in > 75% of cancer cells were considered preserved expression and otherwise considered reduced expression. A comparative investigation was then performed with the clinicopathological data of patients (sex, age, localisation, histological type, depth of invasion, lymph node metastasis, distal metastasis and clinical stage) and cancer-specific survival. The average age of the patients was 64 years old (median 68; range, 32–84 years old). Correlation between the positive rate for each protein and prognosis was determined by the Kaplan-Meier method and multivariate analysis using the Cox regression.

Results

The average observation period was 53 months (median, 48; range, 4–110 months), and 18 patients died during the analysis. The primary localisation of the tumor was the duodenum (n=20), jejunum (n=25), and ileum (n=5). Forty-one cases were well differentiated; 5, poorly differentiated; and 4, mucinous adenocarcinoma. In terms of TNM classification, 14 cases were stage I; 13, stage II; 10, stage III; and 13, stage IV. The positive rates for each protein were CD44, 54%; CD44v6, 50%; and CD44v9, 52%. CD44 and CD44 isoforms were significantly associated with lymph node metastasis and distal metastasis. There was a mutual interrelationship between CD44, CD44v6 and CD44v9 expression. CD44 and CD44v6 immunostaining significantly correlated with abnormal reduced membranous β-catenin staining. CD44 and CD44v9 immunostaining significantly correlated with reduced membranous E-cadherin staining. Factors showing a significant correlation with cancer-specific survival in univariate analysis included lymph node metastasis, distant metastasis, CD44, CD44v6, and CD44v9. In multivariate analysis performed by introducing lymph node metastasis and CD44, CD44v6, and CD44v9 expression in the Cox proportional hazards model, both lymph node status (hazard ratio: 18.5) and CD44 expression (hazard ratio: 7.5) retained independent prognostic significance.

Conclusion

These results suggest that CD44 and CD44 variant isoforms expression are associated with epithelial-mesenchymal transition and could be prognostic factors independent of lymph node metastasis in SBA.

CLINICOPATHOLOGICAL SIGNIFICANCE OF CD44 AND CD44 VARIANT ISOFORMS EXPRESSION IN SMALL BOWEL ADENOCARCINOMA

Hanami Machida 1, Atsushi Tatsuguchi 1, Ryosuke Inoue 1, Yuka Shimazu 1, Ryohei Hamkubo 1, AITOSHI HOSHIMOTO 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Syu Tanaka 1, Shunji Fujimori 1, Katsuhiko Iwakiri 1

1 Nippon Medical School, Tokyo, Japan

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Challenges in upper GI and small bowel cancer (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Small bowel adenocarcinoma (SBA) are rare, but their incidence is increasing. Early diagnosis of SBA remains elusive, so that about one-third of patients are initially diagnosed with distant metastases. In clinical practice, regimens used for SBA parallel those commonly administered in the adjuvant setting for colorectal cancer, owing to its anatomic proximity. However, genomic profiling of SBA has been shown to be distinct from colorectal cancer through comprehensive analysis of genomic alterations. Therefore, it is vital to establish a distinct chemotherapy regimen for SBA based on its molecular pathological characteristics. Claudin-18 plays a key role in constructing tight junctions and altered claudin-18 expression has been documented in various human malignancies. On the basis of this, both monoclonal antibodies and claudin-18.2-specific chimeric antigen receptor engineered T-cells have been recently developed and employed in several clinical trials, showing promising results in the treatment of advanced gastroesophageal and pancreatobiliary tract cancers. However, little is known about the clinicopathological significance of claudin-18 expression in SBA.

Aims & Methods

To explore the localization of claudin-18 in human SBA tissue and draw comparisons and determine the relationship between their expression and clinicopathological factors, and genomic alterations.
We examined 50 surgical resections from patients with primary SBA for immunohistochemical analyses of claudin-18, CK7, CK20, CD10, CDX2, MUC2, MUC5AC, and MUC6 expression. DNA mismatch repair (MMR) status was defined by immunostaining for all MMR proteins; MLH1, MSH2, MLH6, and PMS2. Both MUC 2 and CD10 are markers of intestinal type tumors, whereas MUC5AC and MUC6 are markers of gastric type tumors. Tissue samples showing both gastric and intestinal phenotypes were classified as gastrointestinal type tumors, whereas those showing neither gastric nor intestinal phenotype expression were classified as null type tumors. In addition, genomic profiling was performed on 31 patients using targeted next-generation sequencing.

Results

Claudin-18 expression was observed in 46% of SBA patients. Claudin-18 expression was positively associated with cytokeratin 7 (P=0.003) and MUC5AC (P=0.020) expression, whereas it was negatively associated with MUC2 (P=0.010), CD10 (P=0.014), and CDX2 (P=0.003) expression. Tumor mucin phenotypes included gastric type (n=9), intestinal type (n=20), gastrointestinal type (n=17) and null type (n=4). Claudin-18 was more frequently expressed in gastric type (100%) than in intestinal type (30%) phenotypes (P=0.001). GNAS mutations (N=4) were found in only claudin-18 positive SBA patients, although the difference was not significant. Claudin-18 expression did not correlate with patient age at diagnosis, patient gender, site, histological type, depth of invasion, lymph node metastasis, distal metastasis, TNM stage, and MMR status. However, claudin-18 expression correlated with worse progression free survival.

Conclusion

Claudin-18 expression is associated with gastric immunophenotype and with worse progression free survival. These findings suggest that claudin-18 may be a potential therapeutic target in certain SBA cases.

CLINICOPATHOLOGICAL SIGNIFICANCE OF CLAUDIN-18 EXPRESSION IN SMALL BOWEL ADENOCARCINOMA

Hanami Machida 1, Atsushi Tatsuguchi 1, AITOSHI HOSHIMOTO 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Katsuhiko Iwakiri 1

1 Nippon Medical School, Tokyo, Japan

Conference

UEG Week Copenhagen 2023

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

PP 03 Small intestinal (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Small bowel cancers are rare, accounting for less than 5% of gastrointestinal cancers, but their incidence is increasing. Small bowel adenocarcinoma (SBA) accounts for one-third of small bowel cancers, and due to its rarity, scarcedata exist on its molecular and clinicopathological features.According to the stem cell hypothesis, only a very small number of cancer cells in a tumor have the ability to promote its growth and development. Lgr5 is known as a Wnt/β-catenintarget gene, marking normal stem cells in various tissues, including the small and large intestine. Lgr5 expression has been shown to correlate with poor prognosis in colorectal cancer. However, the clinicopathological significance of Lgr5expression in SBA remains unclear.

Aims & Methods

Aims: To explore the localisation of Lgr5 in human SBA tissueand draw comparisons and determine the relationship between their expression and clinicopathological factors and Wnt/β-catenin signaling pathway-related genomic alterations and proteins.
Methods: We examined 50 surgical resections from patients with primary SBA for immunohistochemical analyses of Lgr5, cyclin D1, c-Myc, and β-catenin expression. DNA mismatch repair (MMR) status was defined by immunostaining for all MMR proteins; MLH1, MSH2, MLH6, and PMS2. A comparative investigation was then performed with the clinicopathological data of patients (sex, age, localisation, histological type, depth of invasion, lymph node metastasis, distant metastasis, and clinical stage) and cancer specific survival. In addition, genomic profiling was performed on 31 patients using targeted next-generation sequencing. Correlation between the positive rate for each protein and prognosis was determined by the Kaplan-Meier method and multivariate analysis using the Cox regression.

Results

The average observation period was 53 months (median, 48; range, 4–110 months), and 18 patients died during the analysis. The primary localisation of the tumor was the duodenum (n=20), jejunum (n=25), and ileum (n=5). Forty-onecases were well differentiated; 5, poorly differentiated; and 4, mucinous adenocarcinoma. In terms of TNM classification, 25cases were stage I; 16, stage II; 12 stage III; and 16, stage IV.Lgr5 expression was observed in 38% of SBA patients andcorrelated with lymph node metastasis, distal metastasis, and advancing TNM stage. Lgr5 expression was not associated with DNA mismatch repair status. Lgr5 expression was significantly associated with reduced membranous β-catenin staining, which correspond to an activation of the Wnt/β-catenin pathway in cancer cells. CTNNB1 mutations (N=3) were found in only Lgr5 positive SBA patients, although the difference was notsignificant (P=0.090). APC mutations (N=5) were not associated with Lgr5 expression. Lgr5 expression, lymph node metastasis, and distant metastasis were significantly associated with worse cancer specific survival. In multivariate analysis for cancer specific survival, lymph node metastasis and Lgr5expression retained independent prognostic significance.

Conclusion

Lgr5 expression is associated with an activation of the Wnt/β-catenin pathway and worse cancer specific survival independent of lymph node metastasis in SBA.

CLINICOPATHOLOGICAL SIGNIFICANCE OF LGR5 EXPRESSION IN SMALL BOWEL ADENOCARCINOMA

Yuka Shimazu 1, Atsushi Tatsuguchi 1, AITOSHI HOSHIMOTO 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Katshiko Iwakiri 1

1 Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan

Conference

UEG Week Vienna 2024

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

Challenges in upper GI and small bowel cancer (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Small bowel adenocarcinoma (SBA) has been shown to have different genomic profiles from gastric or colorectal cancer using comprehensive genomic analysis. Therefore, it is essential to establish chemotherapy based on the characteristics of SBA. Programmed cell death-ligand 1 (PD-L1) expression in SBA is not yet fully understood. In addition, programmed cell death-ligand 2 (PD-L2) has not received as much attention and its role in modulating tumor immunity is unclear. Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes (TILs); therefore, the status of TILs in the tumor microenvironment (TME) may influence its efficacy. The ratio of FoxP3+ T cells to CD8+ T cells has been reported to be useful in predicting the prognosis of digestive system cancers.

Aims & Methods

We investigated the clinicopathological significance of PD-L1 and PD-L2 expression in association with the infiltration of FoxP3+ T cells and CD8+ T cells into the TME to identify PD-L/PD-1 immunotherapy candidates in patients with SBA.
We performed immunohistochemistry for PD-L1, PD-L2, CD8, FoxP3 using formalin-fixed, paraffin-embedded tissue from 50 patients diagnosed with primary SBA. The immunoreactivities of PD-L1 and PD-L2 were determined separately through tumor cells and tumor-infiltrating immune cells (such as lymphocytes and macrophages) throughout the tumor center and invasive margins, and finally evaluated using the combined positive score (CPS). We assessed CD8+ T cells and FoxP3+ T cells in 10 randomly selected microscopic areas of the intratumoral stroma and tumors surrounding the stroma. Subsequently, we calculated and summed the ratio of FoxP3 to CD8+ T cell counts in 10 HPF. Immune-related cell densities were graded as low (≤ median cell counts/mm2 tumor area) or high (> median cell counts/mm2 tumor area).

Results

PD-L1 expression in tumor cells (T-PD-L1) was 34% and in tumor-infiltrating immune cells (I-PD-L1) was 54%. T-PD-L2 was 34% and I-PD-L2 was 42% of cases. PD-L1 CPS ≥ 10 and PD-L2 CPS ≥ 10 were observed in 50% and 56% of cases, respectively. T-PD-L1, I-PD-L1, and PD-L1 CPS ≥ 10 were all associated with deeper depth of invasion (P=0.001, P=0.024, P=0.002). I-PD-L2 expression and PD-L2 CPS ≥ 10 were significantly more common in differentiated types (P=0.015, P=0.030). I-PD-L1 and I-PD-L2 were significantly associated with better CSS (P=0.037, P=0.015). CD8-low was significantly associated with lymph node metastases (P=0.047), distant metastases (P=0.024), peritoneal dissemination (P=0.034), and TNM stage (P=0.047). The CD8-high group had a better prognosis than the CD8-low group (P=0.018). FoxP3-high was not associated with any clinicopathological factor or prognosis. We found that patients with PD-L2 CPS ≥ 10 had worse prognosis in the FoxP3/CD8-low group, although the difference was not significant (P=0.088).

Conclusion

It was suggested that the clinicopathological significance of PD-L1 and PD-L2 expression differs depending on the TME status. The PD-L/PD-1 pathway may contribute to poor prognosis in patients with a low tumor FoxP3/CD8 ratio. PD-L2 may be a better prognostic marker than PD-L1, and immune checkpoint inhibitors may improve prognosis in these cases.

IDENTIFYING IMMUNOTHERAPY CANDIDATES AMONG PATIENTS WITH SMALL BOWEL ADENOCARCINOMA BASED ON CLINICOPATHOLOGICAL SIGNIFICANCE OF PROGRAMMED CELL DEATH-LIGAND EXPRESSION

Yuto Shinagawa 1, AITOSHI HOSHIMOTO 1, Atsushi Tatsuguchi 1, Takayoshi Nishimoto 1, Jun Omori 1, Naohiko Akimoto 1, Katsuhiko Iwakiri 1

1 Nippon Medical School, Tokyo, Japan

Conference

UEG Week Copenhagen 2023

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

PP 03 Small intestinal (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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