1. The Hepatobiliary Cystoadenoma and Cystadenocarcinoma Study for K-ras and P53 genes Jae Won Joh, Sung Joo Kim, Dae Kyum Kim, In Seok Choi, Kwang Woong Lee, Yong Il Kim, Byung Boong Lee, Dae Shick Kim*, Cheol Keun Park * Department of Surgery and Diagnostic Pathology*, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea Introduction Conclusions The hepatobiliary cystadenoma and cystadenocarcinoma are very rare and the pathogenesis of the tumors are still unclear. Recently, they are divided into two groups, according to the presence or absence of ovarian stroma. The ovarian stroma may be suggested as a premalignant lesion. Basically, their histologic features are similar to those of cystadenoma and cystadenocarcinoma of the ovary and pancreas. K-ras and P53 gene mutation are detected in the ovarian and pancreatic cystadenoma and cystadenocarcinoma and proposed as one of the tumorogenic mechanisms. However, they are not studied in the hepatobiliary cystadenoma and cystadenocarcinoma. We experienced these rare tumors including serous cystadenocarcinoma which is very rare, and investigated K-ras and P53 gene. Patients and Methods From Oct.1994 to Dec.1999 We experienced two hepatobiliary cystadenoma and two cystadenocarcinoma, including a serous cystadenocarcinoma which is extremely rare tumor. They are reviwed retrospectively. K-ras and P53 genes analysis DNA was extracted by deparaffinization and digestion from previously fixed and paraffin embedded tissue, and PCR-SSCP analysis was performed. Direct sequencing was performed by dideoxy ‘1’1-termination method using a CircumVent Thermal Cycle Dideoxy DNA sequencing kit. Results 1.Clinical Features of the Cystadenoma Clinical findings Sex/AgeSymptoms Case 1 F/49 No symptom and sign Case 2 F/54 No symptom and sign Serum tumor marker CA 19-9 (U/ml)CEA (ng/ml) AFP (ng/ml) Case 1 117.8 2.2 3.0 Case 2 10.0 1.4 0.2 Radiologic findings US findings Case 1Round anechoic cyst with focal calcification Case 2Lobulating contoured cyst with multiple septum CT findings Case 1Non-enhancing thick walled cyst Case 2Lobulating low attenuated cyst with septa 2. Clinical Features of the Cystadenocarcinoma Clinical findings Sex/AgeSymptoms Case 3 M/64 Abdominal pain Case 4 F/33 Abdominal Pain Serum tumor marker CA 19-9 (U/ml)CEA (ng/ml) AFP (ng/ml) Case 3 0.1 2.8 0.1 Case 4 1.0 1.0 1.0 Radiologic findings (Fig.1) CT findings Case 3Lobulating contoured & low attenuation cystic mass with septa Case 4Necrotic well enhacing solid mass wirh daught nodule Angiography Case 3- Case 4Hypervascular large mass 3. Operations Operation Specific findings Case 1Right lobectomy Case 2 S7 segmentectomy Case 3Lateral segmentectomy Case 4Extended right lobectomy Another mass in diaphragm Partial resection of diaphragmNo mass in pancreas and ovaries 4. Pathologic Findings (Fig.2) Gross examination SizeGross finding Case 1 4 cm Multilocular cyst Case 2 5X2 cmMultilocular cyst Case 3 5.5X5 cm Multilocular cyst with papillary growing mass Case 418.4X14.2 cmMultiple microcysts 11.5X8.5 cm Solid ovoid mass of diaphragm Microscopic examination Diagnosis Epithelial cell lining Ovarian stroma Case 1Mucinous cystadenoma Columnar or Cuboidal + Case 2Mucinous cystadenomaColumnar or Cuboidal - Case 3 Mucinous cystadenocarcinomaColumnar _ Case 4 Serous cystadenocarcinoma withCuboidal - Diaphragmatic leiomyosarcoma Hepatobiliary cystadenoma and cystadenocarcinoma may have a good prognosis with surgical resection. K-ras and P53 gene may not be related to the oncogenesis of hepatobiliary cystadenocarcinoma but further investigation will be needed. 5. K-ras and P53 genes Mutataion of K-ras gene Mutation of P53 gene Case 1- - Case 2- - Case 3- - Case 4- - 6. Postoperative course Postoperative complicationFollow-up time/Condition Case 1None30 months/Non-recurrence Case 2None 6 months/Non-recurrence Case 3None28 months/Non-recurrence Case 4 Intestinal obstruction* 8 months/Non-recurrence * At 5 th postoperative months, she was explored due to intestinal obstuction and small bowel segmental resection was performed. There was no recurrence evidence in intraabdomen. Mass CHA SPA Liver Fig. 1 CT and Angiography of cystadenocarcinoma. Lubulating cystic mass with septa was shown (Left, Case 3). Huge necrotic mass was revealed in right lobe (Middle, Case 4). Angiography showed hypervascular mass (Right, Case 4). CHA; Common hepatic artery, SPA; Splenic artery. Fig 2. A case of serous cystadenocarcinoma. On gross finding, cyst was composed of multiple mictocysts. (Left) On microscopic findings (Right), epithelial lining was composed of cuboidal cells (H & E, X200) and EMA staining showed positive in epithelial cells (Small box, Brown colored cells, EMA stating, X100)