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中华结直肠疾病电子杂志

中华结直肠疾病电子杂志 ›› 2024, Vol. 13 ›› Issue (03) : 229 -235. doi: 10.3877/cma.j.issn.2095-3224.2024.03.008

论著

结直肠印戒细胞癌的临床病理特征研究
王龙1, 武帅1, 王炳智1, 郑波1, 李文斌1, 邹霜梅1,†()   
  1. 1. 100021　北京，国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院病理科
  • 收稿日期:2024-03-27 出版日期:2024-06-25
  • 通信作者: 邹霜梅

Clinicopathological characteristics of colorectal signet-ring cell carcinoma (SRCC)

Long Wang1, Shuai Wu1, Bingzhi Wang1, Bo Zheng1, Wenbin Li1, Shuangmei Zou1,†()   

  1. 1. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
  • Received:2024-03-27 Published:2024-06-25
  • Corresponding author: Shuangmei Zou
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引用本文：

王龙, 武帅, 王炳智, 郑波, 李文斌, 邹霜梅. 结直肠印戒细胞癌的临床病理特征研究[J]. 中华结直肠疾病电子杂志, 2024, 13(03): 229-235.

Long Wang, Shuai Wu, Bingzhi Wang, Bo Zheng, Wenbin Li, Shuangmei Zou. Clinicopathological characteristics of colorectal signet-ring cell carcinoma (SRCC)[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2024, 13(03): 229-235.

目的

印戒细胞癌（SRCC）是结直肠癌中预后极差且临床治疗效果欠佳的特殊亚型。由于相对少见，目前对其临床病理特征尤其是免疫微环境的表达特征尚不清楚。

方法

本研究入组中国医学科学院肿瘤医院79例SRCC病例并以156例管状腺癌（TC）病例作为对照组，收集临床病理资料及预后信息，并进行免疫微环境相关的免疫组化标记染色，比较两组差异。

结果

与TC组相比，SRCC更多见于≤60岁人群（χ2=12.35，P<0.01），发生部位多见于乙状结肠/直肠（χ2=10.91，P<0.01），T分期、N分期及M分期更晚（P值均<0.01），常见脉管瘤栓（χ2=24.16，P<0.01），预后较差（HR=4.19，P<0.01），而且进展方式主要以腹腔播散为主而较少发生远处转移。免疫微环境上PD-L1表达低，但巨噬细胞数量显著增多（P值均<0.01）。

结论

结直肠SRCC是一种恶性程度高的组织学亚型，具有独特的生物学行为及免疫微环境表达特点。

关键词: 结直肠肿瘤, 印戒细胞癌, 病理, 免疫治疗
Objective

Signet-ring cell carcinoma (SRCC) is a special subtype of colorectal cancer with extremely poor prognosis and poor clinical treatment effect. Due to its relative rarity, the expression signature of its clinicopathological features, especially the immune microenvironment, is currently unknown.

Methods

In this study, seventy-nine SRCC cases were enrolled in Cancer Hospital Chinese Academy of Medical Sciences and 156 tubular adenocarcinoma (TC) cases were matched. Clinical and pathological data and prognosis information were collected, and immunohistochemical markers related to immune microenvironment were stained to compare the differences between the two groups.

Results

SRCC was more likely to occur ≤60 years old (χ2=12.35, P<0.01), proximal colon (χ2=10.91, P<0.01). T、N、M stage of SRCC was later (all P<0.01) and more likely to harbour tumor thrombus (χ2=24.16, P<0.01). The prognosis (PFS) is poor (HR=4.19, P<0.01), and the mode of SRCC progression is mainly peritoneal dissemination but less distant metastasis.The presence of CD8+ T on the immune microenvironment showed fewer cells and low PD-L1 expression, but significantly increased numbers of macrophages (all P<0.01).

Conclusion

Colorectal SRCC is a highly malignant histological subtype with unique biological behavior and immune microenvironment characteristics.

Key words: Colorectal neoplasms, Signet-ring cell carcinoma, Pathology, Immunotherapy
图1 镜下图像。1A：典型的SRCC形态；1B：SRCC伴有少量间质黏液；1C：CD8+T细胞数量较少；1D：PD-L1 CPS=0；1E：肿瘤内间质中CD68；1F：肿瘤内间质中CD168；1G：SATB2弱阳性；1H：MET阴性；1I：HER2阴性。（DAB 200X）
表1 TC组与SRCC组临床病理特征比较[例（%）]
临床特征 分组 χ2值 P值
TC（n=156） SRCC（n=79）
性别 0.31 0.579
女 53（33.97） 24（30.38）
男 103（66.03） 55（69.62）
年龄（岁） 12.35 <0.001*
≤60 75（48.08） 57（72.15）
>60 81（51.92） 22（27.85）
位置 10.91 0.004*
乙状结肠/直肠 126（80.76） 49（62.03）
右半结肠 15（9.62） 19（24.05）
左半结肠/横结肠 15（9.62） 11（13.92）
T分期 37.68 <0.001*
T1 14（8.97） 2（2.53）
T2 29（18.59） 4（5.06）
T3 72（46.15） 20（25.32）
T4 41（26.28） 53（67.09）
N分期 64.87 <0.001*
N0 84（53.85） 12（15.19）
N1 44（28.21） 11（13.92）
N2 28（17.95） 56（70.89）
M分期 11.33 0.001*
M0 152（97.44） 68（86.08）
M1 4（2.56） 11（13.92）
脉管瘤栓 24.16 <0.001*
无 127（81.41） 40（50.63）
有 29（18.59） 39（49.37）
图2 PFS生存分析结果。2A：TC组和SRCC组两组的整体PFS生存分析结果；2B：两组T1/T2期PFS生存分析结果；2C：两组T3/T4期PFS生存分析结果
图3 SRCC组和TC组免疫微环境标志物表达的比较（CD8、CD68、PD1、CPS、GZMB、CD163单位：平均阳性数/mm2）
表2 SRCC组和TC组肿瘤细胞的免疫组化结果比较[例（%）]
指标 分组 χ2值 P值
TC（n=111） SRCC（n=60）
HER2 28.38 0.033
- 93（83.78） 57（95.00）
+ 18（16.22） 3（5.00）
C-MET 96.94 <0.001
0 16（14.41） 33（55.00）
1+ 15（13.51） 22（36.67）
2+ 68（61.26） 5（8.33）
3+ 12（10.81） 0
SATB2 4.74 0.030
- 12（10.81） 14（23.33）
+ 99（89.19） 46（76.67）
MMR 4.93 0.248
pMMR 110（99.10） 58（96.67）
dMMR 1（0.90） 2（3.33）
表3 SRCC和TC免疫细胞的免疫组化结果比较
指标 中位数（Q25，Q75） Z值 P值
CD8 -1.246 0.213
TC 1.927（0.972，3.544）
SRCC 2.146（1.137，5.399）
GZMB -6.939 <0.001
TC 0.159（0.091，0.372）
SRCC 0.796（0.402，1.609）
GZMB/CD8 -3.873 <0.001
TC 0.101（0.044，0.257）
SRCC 0.299（0.120，0.532）
CD68 -9.099 <0.001
TC 0.447（0.183，1.444）
SRCC 8.541（4.487，14.223）
CD163 10.501 <0.001
TC 3.851（1.385，9.662）
SRCC 0.029（0.001，0.148）
CD163/CD68 9.448 <0.001
TC 5.576（2.308，13.020）
SRCC 0.003（0.001，0.020）
PD1 5.183 <0.001
TC 4.427（0.232，18.600）
SRCC 0.259（0.001，1.376）
PD-L1 CPS评分 2.944 <0.001
TC 0（0，5）
SRCC 0（0，0）
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