Diagnostic accuracy and prediction increment of markers of epithelial-mesenchymal transition to assess cancer cell detachment from primary tumors

Table 4 Prediction of all-cause mortality after adding continuous or dichotomous E-cadherin measurements to standard diagnostic tests of cancer cell detachment from colorectal primary tumors (n = 188)

	E-cadherin Variable Added to Standard Tests
		Dichotomous E-cadherin Cut Point
	Continuous	0.52	0.60	0.85
C-Index, % (95% CI)^a	66 (58, 72)	51 (41, 59)	54 (45, 62)	56 (48, 63)
Reclassification Metric^b
Number (%) moved to higher risk category	47 (25)	11 (6)	27 (14)	41 (22)
Number (%) moved to lower risk category	55 (29)	93 (49)	83 (44)	70 (37)
Total number (%) reclassified	102 (54)	104 (55)	110 (59)	111 (59)
Reclassification Calibration Statistic P-value	0.1	0.1	0.1	0.2
Event Net Reclassification Index, % (95% CI)	14 (−11, 30)	−22 (−38, −7)	−7 (−23, 10)	3 (−15, 21)
Non-Event Net Reclassification Index, % (95% CI)	13 (3, 35)	54 (44, 63)	41 (29, 52)	24 (12, 37)
Integrated Discrimination Improvement, % (95% CI)	3.4 (1.9, 5.6)	4.3 (2.2, 6.8)	3.4 (1.8, 5.3)	3.7 (1.7, 5.9)

E-cadherin measured on a continuous average intensity scale of 0–3, then modeled as either continuous or dichotomized (EMT positive versus EMT negative) at a given cut point. For dichotomous E-cadherin, EMT positive status was expression below the cut point while EMT negative status was expression at or above the cut point. 62 subjects died within 5 years of diagnosis
^aEach c-index value in the table is for a Cox model estimating 5-year risk of all-cause mortality based on standard diagnostic tests of cancer cell detachment (lymph node evaluation and radiologic imaging) plus the respective continuous or dichotomous E-cadherin variable. C-index for a model of standard diagnostic tests only was 45% (95% CI 36%, 53%)
^bReclassification metrics compare a Cox model estimating 5-year risk of all-cause mortality based on standard diagnostic tests of cancer cell detachment (lymph node evaluation and radiologic imaging) to a Cox model based on standard diagnostic tests plus continuous or dichotomous E-cadherin status defined by a given cut point. Mortality risk categories were 0 – 20%, 20 – 30%, 30 – 40%, and > 40%

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