Detection of extrapancreatic nerve plexus invasion of pancreatic adenocarcinoma. Cytokeratin 19 staining and K-ras mutation.
BACKGROUND
Neural invasion is known to be one of the aggressive characteristics of pancreatic adenocarcinoma. However, there have been no systematic studies on intraoperative examination of neural invasion of pancreatic carcinomas after wide dissection of the retroperitoneum, particularly at the surgical margin.


METHODS
We performed intraoperative immunostaining on the frozen sections of several excised plexus specimens, using peroxidase-labeled anti-cytokeratin 19 antibody in 17 cases of resectable pancreatic carcinoma. Postoperatively, we also tried to detect occult micrometastasis by direct sequencing of the K-ras gene in the same samples.


RESULTS
Intraoperative staining for cytokeratin 19 was positive in 4 of 17 (23.5%) cases. Patients with margin-positive neural invasion had significantly worse prognosis than patients who were margin negative (P < 0.05). One patient had micrometastasis in the nerve plexus, revealed by K-ras mutation, whereas neither cytokeratin 19 staining nor postoperative pathological investigation detected involvement of the analyzed portion. In the four patients margin-positive for cytokeratin 19 staining, the diagnosis of neural invasion by cytokeratin 19 staining was in agreement with the K-ras gene analysis.


CONCLUSIONS
Intraoperative staining for cytokeratin 19 is useful for detecting pancreatic cancer involvement of the neural plexus margin. The results can be also utilized as a prognostic indicator during the follow-up period.
Suwa
H
H
Department of Surgery, Otsu Red Cross Hospital, Japan.
Hosotani
R
R
Kogire
M
M
Doi
R
R
Ohshio
G
G
Fukumoto
M
M
Imamura
M
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D000368:Aged; D001483:Base Sequence / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007432:Intraoperative Period; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009420:Nervous System / Q000473:pathology*; D009423:Nervous System Neoplasms / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D013194:Staining and Labeling
D007633:Keratins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)