01 結(jié)直腸癌
結(jié)直腸癌(colorectal cancer, CRC)：胃腸道中常見的惡性腫瘤，包括結(jié)腸癌和直腸癌。癌瘤大多數(shù)為腺癌，少數(shù)為鱗狀上皮癌及粘液癌。結(jié)直腸癌的發(fā)病率從高到低依次為直腸、乙狀結(jié)腸、盲腸、升結(jié)腸、降結(jié)腸以及橫結(jié)腸，近年有向近端（右半結(jié)腸）發(fā)展的趨勢(shì)。其發(fā)病與生活方式、遺傳、大腸腺瘤等關(guān)系密切。發(fā)病年齡趨老年化，男女之比為1.65:1。
02 結(jié)直腸癌常用腫瘤標(biāo)志物
Calretinin (CALB2)
MUC2
Ki-67
Ki-67蛋白是增殖的細(xì)胞標(biāo)志物，與細(xì)胞增殖密切相關(guān)[8]。其增殖指數(shù)是反映細(xì)胞增殖的特異性指標(biāo)，能比較有效地反映細(xì)胞的過度增殖情況，與腫瘤分化程度、腫瘤浸潤(rùn)深度、區(qū)域淋巴結(jié)轉(zhuǎn)移、臨床分期及預(yù)后有關(guān)[9]。
在結(jié)直腸癌中，p53也是衡量預(yù)后的指標(biāo)之一。結(jié)直腸癌存活率與Ki-67(R=-0.67, p<0.001)和p53(R=-0.64, p<0.001)的表達(dá)都呈負(fù)相關(guān)，Ki-67和p53的過表達(dá)都會(huì)導(dǎo)致預(yù)后不良[10]。 IHC染色定位：主要定位于細(xì)胞核。
GPA33
GPA33(A33)基因編碼A33抗原，A33抗原是免疫球蛋白超家族的I型跨膜糖蛋白，在正常結(jié)腸和小腸上皮細(xì)胞以及95%以上的結(jié)腸癌患者中表達(dá)，在分化良好的腫瘤中尤其明顯，是一種有效的標(biāo)志物[11-12]。有研究提議將GPA33抗體用于放療來治療人GPA-33陽(yáng)性的結(jié)直腸癌[13]。
IHC染色定位：在高分化腫瘤和正常組織中，染色通常是膜性的，但在低分化和黏液性腫瘤中，可能主要是細(xì)胞質(zhì)或細(xì)胞核。
Villin
絨毛蛋白(Villin)是一種actin結(jié)合蛋白，在腸上皮細(xì)胞表達(dá)，調(diào)控結(jié)直腸癌的上皮-間質(zhì)轉(zhuǎn)化(EMT)，也參與上皮細(xì)胞微絨毛的維持，在結(jié)直腸腺癌中陽(yáng)性率達(dá)93%，癌細(xì)胞胞質(zhì)彌漫強(qiáng)(+)伴刷狀緣著色加重[14]。研究表明，Villin表達(dá)缺失是低分化結(jié)腸癌的一個(gè)特征，尤其是微衛(wèi)星不穩(wěn)定(MSI)腫瘤，并與生存率低有關(guān)[14]。
IHC染色定位：細(xì)胞質(zhì)。
CK7(KRT7) / CK20(KRT20)
CK7是一種在腸上皮細(xì)胞中表達(dá)的細(xì)胞角蛋白，在包括結(jié)腸在內(nèi)的許多組織中表達(dá)，在結(jié)腸中其表達(dá)僅限于腺細(xì)胞。CK20是在結(jié)腸直腸隱窩中的上皮細(xì)胞中表達(dá)的角蛋白，該蛋白的表達(dá)水平從隱窩底部（不存在）到頂部逐漸增加，經(jīng)常被用作結(jié)腸中的一種分化標(biāo)記[15]。
大多數(shù)結(jié)直腸癌呈CK7完全陰性/CK20胞質(zhì)彌漫強(qiáng)陽(yáng)性，約20%呈CK7(+)/CK20(+)，因此CK7/CK20組合應(yīng)用有助于結(jié)直腸腺癌的鑒別診斷。CK7和CK20在結(jié)直腸癌的表達(dá)隨組織學(xué)分級(jí)和腫瘤部位的不同而不同[16-18]。
雖然大多數(shù)腫瘤具有高水平的CK20，但在侵襲性、低分化的結(jié)直腸腫瘤和MSI發(fā)生率高的結(jié)直腸腫瘤中可能呈陰性染色[16, 19]。而在侵襲性強(qiáng)、預(yù)后差的BRAF突變的微衛(wèi)星穩(wěn)定型結(jié)直腸癌中，CK7的表達(dá)水平高于其他典型陰性亞型[20]。
IHC染色定位：細(xì)胞質(zhì)。
03 博奧森IHC Kit驗(yàn)證數(shù)據(jù)
常見腫瘤標(biāo)志物即用型IHC Kit產(chǎn)品
參考文獻(xiàn)
1.VONLANTHEN, Silvia, et al. Heterozygosity of SNP513 in intron 9 of the human calretinin gene (CALB2) is a risk factor for colon cancer. Anticancer research, 2007, 27.6C: 4279-4288.
2.GOTZOS, Vassilis, et al. Selective distribution of calretinin in adenocarcinomas of the human colon and adjacent tissues. The American journal of surgical pathology, 1999, 23.6: 701-711.
3.WINN, Brody, et al. Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Human pathology, 2009, 40.3: 398-404.
4.LIN, Fan, et al. Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Archives of Pathology and Laboratory Medicine, 2014, 138.8: 1015-1026.
5.BETGE, Johannes, et al. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Archiv, 2016, 469: 255-265.
6.MOEHLE, Christoph, et al. Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease. Journal of molecular medicine, 2006, 84: 1055-1066.
7.VELCICH, Anna, et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science, 2002, 295.5560: 1726-1729.
8.SCHOLZEN, Thomas, et al. The Ki‐67 protein: from the known and the unknown. Journal of cellular physiology, 2000, 182.3: 311-322.
9.MELLING, Nathaniel, et al. High Ki67 expression is an independent good prognostic marker in colorectal cancer. Journal of clinical pathology, 2016, 69.3: 209-214.
10.LUMACHI, Franco, et al. Expression of p53 and Ki-67 as prognostic factors for survival of men with colorectal cancer. Anticancer research, 2012, 32.9: 3965-3967.
11.HEATH, Joan K., et al. The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily. Proceedings of the National Academy of Sciences, 1997, 94.2: 469-474.
12.BAPTISTELLA, Antuani R., et al. Heterogeneous expression of A33 in colorectal cancer: possible explanation for A33 antibody treatment failure. Anti-cancer drugs, 2016, 27.8: 734-737.
13.CHEAL, Sarah M., et al. Curative multicycle radioimmunotherapy monitored by quantitative SPECT/CT-based theranostics, using bispecific antibody pretargeting strategy in colorectal cancer. Journal of Nuclear Medicine, 2017, 58.11: 1735-1742.
14.ARANGO, Diego, et al. Villin expression is frequently lost in poorly differentiated colon cancer. The American journal of pathology, 2012, 180.4: 1509-1521.
15.MOLL, Roland, et al. Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. The Journal of cell biology, 1990, 111.2: 567-580.
16.HARBAUM, Lars, et al. Keratin 20-a diagnostic and prognostic marker in colorectal cancer?. 2012.
17.HARBAUM, Lars, et al. Keratin 7 expression in colorectal cancer–freak of nature or significant finding?. Histopathology, 2011, 59.2: 225-234.
18.何建芳等. 實(shí)用免疫組化病理診斷. 2018.
19.MERLOS-SUáREZ, Anna, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell stem cell, 2011, 8.5: 511-524.
20.LANDAU, Michael S., et al. BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression. Human pathology, 2014, 45.8: 1704-1712.
往期精彩
