Recent advances of cluster of differentiation 74 in cancer

Table 1 Expression levels and clinical significance of cluster of differentiation 74 in human cancers

Cancer type	Event	Method	Ref
Renal cell cancer	CD74 was detected in 53 of 60 (88.3%) renal cell cancer tissues	IHC	[90, 91]
	CD74 is a useful diagnostic marker for distinguishing clear cell RCC from chromophobe and oncocytoma RCC	IHC	[92]
	CD74 was upregulated in 34 of 40 (85.0%) of clear cell RCC tissues compared with the corresponding normal kidney tissues, and the expression level was positively correlated with VEGF-D (Pearson’s correlation, r = 0.65, P < 0.001)	Quantitative real-time RT-PCR, IHC	[49]
Malignant fibrous histiocytoma Thymic epithelial neoplasm	Differential expression of CD74 was found in atypical malignant fibrous histiocytoma (90% positive) and fibroxanthoma (10% positive), suggesting that CD74 may be a marker of tumor progression	IHC	[93]
	CD74 was detected in 88% (15/17) of thymic carcinomas, 70% (14/20) of invasive thymomas, but only 33% (9/27) of benign thymomas (9/27), suggesting that CD74 is a useful marker for the classification of thymic epithelial neoplasms	IHC	[94]
Colorectal cancer	A linear increase of CD74 expression was found in the progression from low- to high-grade invasive cancer tissues	IHC	[95]
	High levels of CD74 were detected in 23 of 156 (15.0%) curatively resected colorectal cancer tissues	IHC	[96]
	CD74 was increased in dysplastic epithelial cells in 47 of 55 (85%) human colorectal adenomas, with CD74 and MIF protein levels together predicting increasing dysplasia in individual adenomas (P = 0.003)	IHC	[97]
Gastric cancer	CD74 was detected in 48 of 126 (38.1%) gastric cancer tissues, and the expression was negatively correlated with the depth of invasion and HLA-DR expression. The patients with detectable CD74 show poor surgical outcomes (P < 0.05) CD74 was detected in 39 of 58 (67.2%) gastric carcinoma tissues, showing significant correlation with the differentiation of gastric carcinoma (P < 0.05)	IHC IHC	[98] [99]
Breast cancer	The expression of CD74 was significantly more abundant in invasive or metastatic tumors than in ductal carcinoma in situ (P = 0.02 and P = 0.05, respectively)	SAGE	[100]
	CD74 was detected in 468 of 580 (80.7%) breast cancer tissues, and was related to lymph node metastasis and triple-negative breast cancer (P = 0.01 and 0.001). In addition, CD74 expression had a linear correlation with lymph node metastasis and triple-negative breast cancer (P = 0.02 and 0.001)	IHC	[101]
	Stat1 and CD74 overexpression is co-dependent and linked to increased invasion and lymph node metastasis in triple-negative breast cancer	LC-MS/MS, IHC	[102]
	CD74 expression was increased in high-grade, invasive urothelial carcinoma of the bladder		[103]
Multiple myeloma	CD74 was detected in 19 of 22 (86.4%) multiple myeloma tissues	IHC	[69]
Pancreatic cancer	CD74 was identified as an overexpressed gene when compared with two SAGE libraries (6 pancreatic cancers vs 11 non-neoplastic tissues), and the expression of CD74 was detected in 15 of 18 (83%) pancreatic ductal adenocarcinoma tissues	SAGE, IHC	[104]
	CD74 was expressed in 52 of 67 (77.6%) pancreatic cancer tissues that was correlated with high perineural invasion (P < 0.008)	IHC	[105]
	Moreover, 47 of 68 (69.1%) and 21 of 68 (30.9%) pancreas tissues from patients receiving curative extended resection showed lower (< 70%) and higher (≥ 70%) CD74 expression, respectively. Patients with higher CD74 expression in pancreatic cancer tissues showed a higher rate of lymphatic permeation (P = 0.04), perineural invasion (P = 0.01), poor prognosis (P = 0.006), and poor survival (P = 0.003) compared with those with lower expression	IHC	[106]
	Fourteen of 46 (30.4%) and 32 of 46 (69.6%) pancreatic ductal adenocarcinoma tissues showed lower (< 25%) and higher (≥ 25%) CD74 expression, respectively. Patients with higher CD74 expression in pancreatic cancer tissues showed a higher rate of perineural invasion (P = 0.007) and poor 3- and 5-yr cumulative survival rates (41% and 62% vs 0% and 9%, P = 0.000) compared with those with lower expression	IHC	[107]
Cervical squamous cell carcinoma	CD74 expression was significantly higher in CIN than in the normal samples and higher in SCC than in CIN	IHC	[108]
Urothelial carcinoma of the bladder	CD74 was detected in 192 of 342 (56.1%) urothelial carcinoma of the bladder tissues, which is associated with older age at diagnosis (≥ 68 yr, P = 0.048), high World Health Organization grade (P = 0.019), advanced stages (P = 0.001), non-papillary growth pattern (P = 0.040), the absence of tumor-infiltrating inflammatory cells (P < 0.001), and the presence of tumor-associated inflammatory cells (P = 0.017). However, CD74 expression was not related to recurrence-free and overall survivals in primary and subgroup analyses	IHC	[103]
Non-small cell lung cancer	A case report found a mutation in CD74-ROS1 that is associated with acquired resistance to crizotinib.	FISH, RT-PCR	[109]
	CD74 was detected in 57 of 70 (81.4%) non-small cell lung cancer tissues	IHC	[110]
	CD74-ROS1 fusion transcript was detected in 5 of 1073 (0.5%) non-small cell lung cancer tissues	RT-PCR	[61]
	CD74-ROS1 fusion transcript was detected in 4 of 556 (0.7%) non–small cell lung cancer tissues	IHC	[111]
	CD74-ROS1 fusion transcript was detected in 1 of 114 (0.9%) non–small cell lung cancer tissues	RT-PCR	[56]
	CD74-ROS1 fusion transcript was detected in 2 of 208 (1.0%) never-smokers with lung adenocarcinoma tissues	RT-PCR	[112]
	CD74-ROS1 fusion transcript was detected in 2 of 447 (4.5%) never-smokers with lung adenocarcinoma tissues	Transcriptome sequencing	[113]
	Two CD74 polymorphisms, rs2748249 and rs1560661, are associated with hematologic toxicity in patients with non–small cell lung cancer after platinum-based chemotherapy	BeadChip	[114]

CD74: Cluster of differentiation 74; MIF: Migration inhibitory factor; RCC: Renal cell cancer; IHC: Immunohistochemistry; RT-PCR: Reverse-transcription polymerase chain reaction; SAGE: Serial analysis of gene expression; LC-MS/MS: Liquid chromatography–mass spectrometry/ mass spectrometry; FISH: Fluorescence in situ hybridization.