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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors.

Jung SH, Suh KS, Kang DY, Kang DW, Kim YB, Kim ES - Gut Liver (2011)

Bottom Line: A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05).Two cases showed a silent mutation in exon 18 of PDGFRA.Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea.

ABSTRACT

Background/aims: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST.

Methods: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes.

Results: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA.

Conclusions: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

No MeSH data available.


Related in: MedlinePlus

Gastrointestinal stromal tumors of the small intestine, high-grade, spindle cell type (A, H&E stain, ×400), with liver metastasis within 24 months (B, H&E stain, ×400). Nuclear expression of p16 (C, immunohistochemical stain for p16, ×400) and cell membrane/cytoplasmic staining of DOG1 (D, immunohistochemical stain for DOG1, ×400).
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Figure 2: Gastrointestinal stromal tumors of the small intestine, high-grade, spindle cell type (A, H&E stain, ×400), with liver metastasis within 24 months (B, H&E stain, ×400). Nuclear expression of p16 (C, immunohistochemical stain for p16, ×400) and cell membrane/cytoplasmic staining of DOG1 (D, immunohistochemical stain for DOG1, ×400).

Mentions: Sixty two GISTs (76.5%) were predominantly spindle cell type, 10 (12.3%) were epithelioid-like, and 9 tumors (11.1%) exhibited a mixed pattern. The tumors were classified into very low risk (5 cases, 6.2%), low risk (16 cases, 19.8%), intermediate risk (25 cases, 30.9%), and high risk categories (35 cases, 43.2%) (Table 1).7 The tumor size ranged from 0.3 cm to 24 cm (mean of very low risk group was 1.1 cm; of low risk group was 4.3 cm; of intermediate risk group was 6.6 cm; of high risk group was 11.7 cm). Immunohistochemically, c-kit was positive in 76 (93.8%) of 81 GIST cases, PDGFRA in 75 cases (92.7%), and DOG1 in 77 cases (95.1%). With a cutoff value of 10%, p16 expression was positive in 36 cases (44.4%) and with a cutoff value of 50%, 26 cases were positive (32.1%) (Table 1, Figs. 2 and 3). Among 5 c-kit negative cases, four were DOG+/PDGFRA+ and one was DOG+/PDGFRA- (Table 2). There were no correlations between p16, KIT, DOG1 or PDGFRA expression and the risk of malignancy (p>0.05) (Table 3). However, a correlation between p16 expression and recurrence and/or metastasis was demonstrated (p<0.05). Negative DOG1 expression was correlated with recurrence and/or metastasis (p<0.05) (Table 4).


Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors.

Jung SH, Suh KS, Kang DY, Kang DW, Kim YB, Kim ES - Gut Liver (2011)

Gastrointestinal stromal tumors of the small intestine, high-grade, spindle cell type (A, H&E stain, ×400), with liver metastasis within 24 months (B, H&E stain, ×400). Nuclear expression of p16 (C, immunohistochemical stain for p16, ×400) and cell membrane/cytoplasmic staining of DOG1 (D, immunohistochemical stain for DOG1, ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3140662&req=5

Figure 2: Gastrointestinal stromal tumors of the small intestine, high-grade, spindle cell type (A, H&E stain, ×400), with liver metastasis within 24 months (B, H&E stain, ×400). Nuclear expression of p16 (C, immunohistochemical stain for p16, ×400) and cell membrane/cytoplasmic staining of DOG1 (D, immunohistochemical stain for DOG1, ×400).
Mentions: Sixty two GISTs (76.5%) were predominantly spindle cell type, 10 (12.3%) were epithelioid-like, and 9 tumors (11.1%) exhibited a mixed pattern. The tumors were classified into very low risk (5 cases, 6.2%), low risk (16 cases, 19.8%), intermediate risk (25 cases, 30.9%), and high risk categories (35 cases, 43.2%) (Table 1).7 The tumor size ranged from 0.3 cm to 24 cm (mean of very low risk group was 1.1 cm; of low risk group was 4.3 cm; of intermediate risk group was 6.6 cm; of high risk group was 11.7 cm). Immunohistochemically, c-kit was positive in 76 (93.8%) of 81 GIST cases, PDGFRA in 75 cases (92.7%), and DOG1 in 77 cases (95.1%). With a cutoff value of 10%, p16 expression was positive in 36 cases (44.4%) and with a cutoff value of 50%, 26 cases were positive (32.1%) (Table 1, Figs. 2 and 3). Among 5 c-kit negative cases, four were DOG+/PDGFRA+ and one was DOG+/PDGFRA- (Table 2). There were no correlations between p16, KIT, DOG1 or PDGFRA expression and the risk of malignancy (p>0.05) (Table 3). However, a correlation between p16 expression and recurrence and/or metastasis was demonstrated (p<0.05). Negative DOG1 expression was correlated with recurrence and/or metastasis (p<0.05) (Table 4).

Bottom Line: A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05).Two cases showed a silent mutation in exon 18 of PDGFRA.Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea.

ABSTRACT

Background/aims: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST.

Methods: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes.

Results: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA.

Conclusions: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

No MeSH data available.


Related in: MedlinePlus