[655] Optimal Immunohistochemical Panel for Distinguishing Esophageal Adenocarcinoma from Squamous Cell Carcinoma

Michael A DiMaio, Shirley Kwok, Kelli D Montgomery, Anson W Lowe, Reetesh K Pai. Stanford University, Stanford, CA

Background: Distinguishing between esophageal adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is often based on standard morphologic criteria. In small biopsies, classification can be difficult, especially for poorly differentiated tumors. We analyzed commonly used immunohistochemical markers and two newly described markers, AGR2 and SOX2, in esophageal ADC and SCC to establish the optimal panel to distinguish these tumors.
Design: Tissue microarrays with 69 esophageal ADC and 41 whole sections of esophageal SCC biopsies (n=27) and excisions (n=14) were stained with p63, CK 5/6, CK7, CDX2, MUC2, MUC5AC, AGR2, and SOX2 and semiquantitatively scored. Sensitivities and specificities were calculated for individual markers and select combinations using the morphologic diagnosis as a gold standard.
Results:

Immunohistochemistry in Esophageal Adenocarcinoma and Squamous Cell Carcinoma

Marker	Diagnosis	Negative (%)	1-50% Reactivity (%)	>50% Reactivity (%)
p63	ADC	62 (90)	7 (10)	0
p63	SCC	0	3 (7)	38 (93)
CK5/6	ADC	60 (87)	9 (13)	0
CK5/6	SCC	1 (2)	1 (2)	39 (96)
SOX2	ADC	45 (65)	13 (19)	11 (16)
SOX2	SCC	6 (15)	7 (17)	28 (68)
CK7	ADC	6 (9)	9 (13)	54 (78)
CK7	SCC	27 (66)	9 (22)	5 (12)
MUC2	ADC	41 (59)	25 (36)	3 (4)
MUC2	SCC	33 (80)	8 (20)	0
MUC5AC	ADC	25 (36)	29 (42)	15 (22)
MUC5AC	SCC	40 (98)	1 (2)	0
CDX2	ADC	28 (41)	27 (39)	14 (20)
CDX2	SCC	30 (73)	5 (12)	6 (15)
AGR2	ADC	1 (2)	5 (7)	63 (91)
AGR2	SCC	26 (63)	11 (27)	4 (10)

Sensitivity and Specificity of Marker Combinations

Marker Reactivity	Predicted Tumor	Sensitivity (%)	Specificity (%)
p63 (any+)	SCC	100	90
CK5/6 (any+)	SCC	98	87
p63 (any+) and CK5/6 (any+)	SCC	98	99
MUC5AC (-) and p63 (any+) and CK5/6 (any+)	SCC	95	99
AGR2 (any+)	ADC	99	63
MUC5AC (any+)	ADC	64	98
AGR2 (any+) and p63 (-) and CK5/6 (-)	ADC	78	100

Among 55 poorly differentiated carcinomas (40 ADC, 15 SCC), the combination most specific (99%) and sensitive (98%) for SCC was p63 (any+) and CK 5/6 (any+) because p63 and CK5/6 in ADC were typically expressed independently of each other. Among poorly differentiated carcinomas, the combination of MUC5AC (-), p63 (any+), and CK5/6 (any+) was 87% sensitive and 98% specific for SCC and the combination of AGR2 (any+), p63 (-), and CK5/6 (-) was 85% sensitive and 100% specific for ADC.
Conclusions: A panel including p63, CK5/6, MUC5AC, and AGR2 is most helpful in differentiating esophageal ADC and SCC, especially in poorly differentiated lesions. The combination of p63 and CK5/6 offers the best sensitivity and specificity for SCC over ADC. AGR2 staining was highly sensitive but not specific for ADC. MUC5AC staining was highly specific but not sensitive for ADC.
Category: Gastrointestinal

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 110, Monday Morning