Arai J, et al. Gut. 2023 May 17;gutjnl-2023-330052. doi: 10.1136/gutjnl-2023-330052.
2023년 Gut 에 실린 짧은 letter 입니다. 올 초에 실린 Rugge M 등이 발표한 AIG와 gastric cancer (GC)의 연관성에 대한 cohort 연구 결과 (홈페이지 최신연구소개 7번) 발표 이후 metaplasia로 진행하는 대표적인 원인인 H. pylori related gastritis (HpG)와 AIG 사이의 carcinogenesis 의 차이에 대하여 앞으로 많은 연구가 나올 것으로 보입니다. 이러한 차원에서 발표된 letter 인데요, 한번 살펴 보도록 하겠습니다.
저자들은 GC환자 중 Anti-parietal cell ab. (APCA)양성 환자 76명에 대한 연구를 발표한 적이 있습니다. (홈페이지 최신연구소개 15번) 이 중에 H. pylori 감염과 연관성이 없는 pure AIG 환자 8명을 대상으로 GC 발생에 대한 histological analyses를 했던 내용입니다.
Table 1. Baseline characteristics and immunohistochemical staining results of patients
Figure 1. Representative images of H&E and immunohistochemical staining for CD3, Ki67, CD44v9 and TROP2 in gastric mucosa of APCA+ andHelicobacter pylori+/APCA− cases. (A) Representative H&E and immunohistochemical staining for CD3, Ki67, CD44v9 and TROP2 in noncancerous gastric mucosa of APCA+ and H. pylori+/APCA− cases. (B) Immunohistochemical staining for Ki67, CD44v9 and TROP2 in gastric mucosa including stomach cancer of APCA+ and H. pylori+/APCA− cases. The noncancerous lesions in H. pylori+ case and cancerous lesions in both groups were diffusely positive for TROP2, whereas noncancerous lesions in APCA+ case had much lower positivity for TROP2. *Tumour lesions, **TROP2 positive lesions. Scale bars, 100 µm. APCA, antiparietal cell antibody.
Precancerous lesions adjacent to cancerous lesions showed a greater intraepithelial infiltration of CD3-positive cells in the APCA+ group compared with the H. pylori+APCA− group (22.75±10.89 vs 10.25±5.52, p=0.008), consistent with T cell-dependent autoimmune reaction.
The precancerous lesions in H. pylori+ cases and cancerous lesions in both groups were diffusely positive for TROP2, whereas precancerous lesions in APCA+ cases had much lower positivity for TROP2 (6/2/0 vs 1/1/6 in grade1/2/3, respectively; p=0.008). Statistically, TROP2 was associated with APCA positivity (80% vs 0%, p=0.007) and fewer CD3-positive cells (20.70±10.66 vs 9.50±5.92, p=0.034).
TROP2 expression reflects the transition from metaplasia to dysplasia in the stomach.
TROP2-negative metaplasia in APCA+ cases was less carcinogenic than TROP2-enriched metaplasia in APCA− H. pylori+ cases.
Because the infiltration of T lymphocytes was negatively correlated with TROP2 expression, autoimmune reactions based on APCA might contribute to the elimination of TROP2+ dysplastic cells from metaplasia.
Trop2 is Upregulated in the Transition to Dysplasia in the Metaplastic Gastric Mucosa
J Pathol. 2020 July ; 251(3): 336–347. doi:10.1002/path.5469.
* Trop2 is a transmembrane glycoprotein encoded by the tumor-associated signal transducer 2 (tacstd2) gene, and was first discovered as a trophoblast surface marker. Trop2 is also known as trophoblast antigen 2, TACSTD2, membrane component 1 surface marker (M1S1), epithelial glycoprotein 1 (EGP-1), and gastrointestinal antigen 733–1 (GA733–1). Trop2 has been shown to promote tumor pathogenesis by activating the MAPK/ERK pathway, and has been identified as a possible therapeutic target in epithelia carcinomas. Trop2 is upregulated in many epithelial human cancers, including breast, colon, non-small-cell lung, gastric, pancreatic, oral and esophageal squamous cell, cervical, ovarian, and gallbladder, and is associated with tumor aggressiveness, metastasis, and worse prognosis.
Arai J, et al. Gut. 2023 May 17;gutjnl-2023-330052. doi: 10.1136/gutjnl-2023-330052.
2023년 Gut 에 실린 짧은 letter 입니다. 올 초에 실린 Rugge M 등이 발표한 AIG와 gastric cancer (GC)의 연관성에 대한 cohort 연구 결과 (홈페이지 최신연구소개 7번) 발표 이후 metaplasia로 진행하는 대표적인 원인인 H. pylori related gastritis (HpG)와 AIG 사이의 carcinogenesis 의 차이에 대하여 앞으로 많은 연구가 나올 것으로 보입니다. 이러한 차원에서 발표된 letter 인데요, 한번 살펴 보도록 하겠습니다.
저자들은 GC환자 중 Anti-parietal cell ab. (APCA)양성 환자 76명에 대한 연구를 발표한 적이 있습니다. (홈페이지 최신연구소개 15번) 이 중에 H. pylori 감염과 연관성이 없는 pure AIG 환자 8명을 대상으로 GC 발생에 대한 histological analyses를 했던 내용입니다.
Table 1. Baseline characteristics and immunohistochemical staining results of patients
Figure 1. Representative images of H&E and immunohistochemical staining for CD3, Ki67, CD44v9 and TROP2 in gastric mucosa of APCA+ andHelicobacter pylori+/APCA− cases. (A) Representative H&E and immunohistochemical staining for CD3, Ki67, CD44v9 and TROP2 in noncancerous gastric mucosa of APCA+ and H. pylori+/APCA− cases. (B) Immunohistochemical staining for Ki67, CD44v9 and TROP2 in gastric mucosa including stomach cancer of APCA+ and H. pylori+/APCA− cases. The noncancerous lesions in H. pylori+ case and cancerous lesions in both groups were diffusely positive for TROP2, whereas noncancerous lesions in APCA+ case had much lower positivity for TROP2. *Tumour lesions, **TROP2 positive lesions. Scale bars, 100 µm. APCA, antiparietal cell antibody.
Precancerous lesions adjacent to cancerous lesions showed a greater intraepithelial infiltration of CD3-positive cells in the APCA+ group compared with the H. pylori+APCA− group (22.75±10.89 vs 10.25±5.52, p=0.008), consistent with T cell-dependent autoimmune reaction.
The precancerous lesions in H. pylori+ cases and cancerous lesions in both groups were diffusely positive for TROP2, whereas precancerous lesions in APCA+ cases had much lower positivity for TROP2 (6/2/0 vs 1/1/6 in grade1/2/3, respectively; p=0.008). Statistically, TROP2 was associated with APCA positivity (80% vs 0%, p=0.007) and fewer CD3-positive cells (20.70±10.66 vs 9.50±5.92, p=0.034).
TROP2 expression reflects the transition from metaplasia to dysplasia in the stomach.
TROP2-negative metaplasia in APCA+ cases was less carcinogenic than TROP2-enriched metaplasia in APCA− H. pylori+ cases.
Because the infiltration of T lymphocytes was negatively correlated with TROP2 expression, autoimmune reactions based on APCA might contribute to the elimination of TROP2+ dysplastic cells from metaplasia.
Trop2 is Upregulated in the Transition to Dysplasia in the Metaplastic Gastric Mucosa
J Pathol. 2020 July ; 251(3): 336–347. doi:10.1002/path.5469.
* Trop2 is a transmembrane glycoprotein encoded by the tumor-associated signal transducer 2 (tacstd2) gene, and was first discovered as a trophoblast surface marker. Trop2 is also known as trophoblast antigen 2, TACSTD2, membrane component 1 surface marker (M1S1), epithelial glycoprotein 1 (EGP-1), and gastrointestinal antigen 733–1 (GA733–1). Trop2 has been shown to promote tumor pathogenesis by activating the MAPK/ERK pathway, and has been identified as a possible therapeutic target in epithelia carcinomas. Trop2 is upregulated in many epithelial human cancers, including breast, colon, non-small-cell lung, gastric, pancreatic, oral and esophageal squamous cell, cervical, ovarian, and gallbladder, and is associated with tumor aggressiveness, metastasis, and worse prognosis.