Placental S100 (S100P) and GATA3: Markers for Transitional Epithelium and Urothelial Carcinoma Discovered by Complementary DNA Microarray

John PT Higgins, Gulsah Kaygusuz, Lingli Wang, Kelli Montgomery, Veronica Mason, Shirley X Zhu, Robert J Marinelli, Joseph C Presti Jr, Matt van de Rijn, James D Brooks

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Figure 1: (full size) Genes highly expressed in urothelial carcinoma. The sample dendrogram at the top of the figure reflects the relative degree to which the samples show similar expression of 8856 genes. Each tumor type shows a reproducible pattern of gene expression that causes them to be grouped together in this dendrogram. One urothelial carcinoma is exceptional in that it is grouped with the renal carcinomas. The heatmap below the dendrogram represents 220 genes that are highly expressed in urothelial carcinomas. Selected gene names are provided to the right of the heatmap and their expression profiles across the samples can be read from the heatmap. Genes for which protein expression was investigated by immunohistochemistry include Tumor protein p73-like (p63), Keratin 5, S100P, and GATA3. These genes are highlighted red.

Figure 2: (full size) Immunohistochemistry. A: S0084 expression in normal urothelium. Both cytoplasmic as well as strong nuclear expression is seen. The basal layer is largely unstained. B: S0084 expression in low grade papillary urothelial carcinoma. Strong staining of the entire epithelium for S0084 is seen while the underlying stroma is negative. C: S0084 expression in high grade, invasive urothelial carcinoma. Pleomorphic, highly irregular nuclei are stained while cytoplasmic staining is weaker. D: Monoclonal S100P staining in low grade urothelial carcinoma. The pattern of staining is essentially identical to that seen for S0084 with both cytoplasmic and nuclear staining. E: Monoclonal S100P staining in high grade urothelial carcinoma. F: GATA3 staining in low grade urothelial carcinoma. There is no significant cytoplasmic staining. G: GATA3 staining in high grade, invasive urothelial carcinoma. H: Typical subset staining pattern of low grade urothelial carcinoma for cytokeratin 5/6. Strong staining is limited to those cells located next to the adjacent stroma. I: Typical, strong, specific nuclear staining of high-grade, invasive urothelial carcinoma for p63.

Table 1: Urothelial carcinoma immunohistochemistry

 

 

S0084

S100Pm

GATA3

p63

CK5/6

Neg

 

46

73

111

42

140

equiv

 

27

21

14

30

30

weak

 

24

49

39

21

98

strong

 

239

193

172

243

68

total cores

336

336

336

336

336

total interpretable

309

315

322

306

306

% positive rate

85.1

76.8

65.5

86.3

54.2

%strong positive

90.9

79.8

81.5

92.0

41.0

Table 2: S100p expression by immunohistochemistry

Carcinoma

% S0084 positive

% S100P positive

Number of cases

Renal urothelial

94

80

17/15

Bladder urothelial

85

77

309/315

Stomach

58

62

19/21

Esophageal adeno

100

60

4/5

Pancreas

67

30

6/10

Colorectal

61

20

72/80

Bladder squamous

0

14

7/7

Hepatocellular

36

14

11/14

Lung

27

10

41/48

Ovary

15

7

40/41

Prostate

3

2

260/256

Adrenal

0

0

3/3

Breast ductal

25

0

4/4

Cervix adeno

25

0

4/5

Cervix squamous

50

0

4/6

Endometrial

7

0

30/31

Esophageal squamous

0

0

7/8

Gallbladder

0

0

1/1

Melanoma

0

0

13/16

Renal cell

1

0

133/137

Seminoma

0

0

10/10

Squamous NOS

19

0

16/20

Thyroid

0

0

14/17

Table 3: GATA3 expression by immunohistochemistry

Carcinoma

% positive

Number of cases

Breast ductal

100

4

Renal urothelial

67

15

Bladder urothelial

59

304

Adrenal

0

3

Bladder squamous cell

0

7

Cervix adeno

0

4

Cervix squamous

0

6

Colorectal

0

71

Endometrial

0

27

Esophageal adeno

0

4

Esophageal squamous

0

8

Gallbladder

0

1

Hepatocellular

0

13

Lung

0

45

Melanoma

0

12

Ovary

0

39

Pancreas

0

6

Prostate

0

257

Renal cell

0

135

Seminoma

0

6

Squamous NOS

0

23

Stomach

0

15

Thyroid

0

18


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