Tumor factors concerned with primary culture of transitional cell carcinomas

We investigated retrospectively tumor factors such as tumor organ, method of tumor collection, tumor morphology and grade, concerned with primary cultures of transitional cell carcinomas of bladder, renal pelvis and ureter. Moreover, we investigated whether chemotherapy before tumor collection influence on the success rate of primary culture. After mechanical disaggregation of specimens from 42 bladder cancers and 11 renal pelvic or ureter cancers, monolayer cultures were carried out. When epithelial growth or colony-formation was observed, we determined that primary culture was succeeded. In total 30 primary cultures out of 53 (56.6%) were successful and tumor organ or method of tumor collection did not influence primary cultures. The success rates in the groups of papillary tumors and non-papillary tumors were significantly different (72.4% and 37.4%, respectively). Culture was more successful with grade 1 tumors. Although intravesical chemotherapy before tumor collection did not influence the success rate of primary culture, one-shot intra-arterial infusion chemotherapy made it worse (p less than 0.05) and it was concerned with histopathological effects according to the classification of Shimosato and Oboshi.     

A clinical survey of renal pelvic and ureteral tumors associated with bladder tumor

A clinical survey was performed on 80 cases of renal pelvic and ureteral transitional cell carcinomas we treated between January, 1963 and December, 1986. The cases included 30 of renal pelvic tumors, 17 of ureteral tumors, 3 of renal pelvic and ureteral tumors, 7 of renal pelvic and ureteral and bladder tumors, 16 of ureteral and bladder tumors and 7 of renal pelvic or ureteral tumors after treatment for bladder tumors. There were 37 cases of bladder tumors: 7 cases with preceding bladder tumors, 23 cases of synchronous bladder tumors, and 13 cases of subsequent bladder tumors. The 5-year survival for all cases was 60.2%. The 5-year survival for 43 cases unrelated with bladder tumors was 80.5% and that for 37 cases of bladder tumor was 41.6%. Therefore, there was a significant difference between these 2 groups (p less than 0.005). The 5-year survival for 50 cases without synchronous bladder tumors at first diagnosis was significantly higher than that for 23 cases with synchronous bladder tumors (p less than 0.001). Subsequent bladder tumors occurred after 2 to 48 months (mean 10 months) of the initial treatment for renal pelvic and ureteral tumors. Six of the 7 cases of preceeding bladder tumors were superficial tumors of pTa and pT1 and 3 cases had vesicoureteral reflux.     

ANALYSIS OF nm23 GENE EXPRESSIONS IN HUMAN BLADDER AND RENAL CANCERS

We measured nm23-H1 and nm23-H2 mRNA levels in tissues from 22 human bladder cancers and 16 renal cell carcinomas, and in 7 bladder cancer and 6 renal cancer cell lines by Northern blot and slot blot hybridization analyses. Differences in mRNA levels were evaluated in primary tumor tissues and in paired normal tissues and cell lines. Moreover, nrh23 gene expression in primary tumor tissues was compared with clinicopathological features. High nm23-H1 and nm23-H2 expression was observed in cancerous areas of human bladder tissue ( nm23-H1 : p = 0.001, nm23-H2 : p = 0.001) and bladder cancer cell lines ( nm23-H1: p = 0.001, nm23-H2: p< 0.001) compared with that in normal bladder mucosa. However, mRNA levels of both nm23 genes were not associated with histological grade, pathological stage, tumor metastasis or prognosis. On the other hand, in human renal cell carcinomas, levels of both nm23 mRNAs in tumor tissues were similar to those in paired normal kidneys, but elevated in cultured cell lines ( nm23-H1: p= 0.002, nm23-H2: p = 0.014). Moreover, there was a tendency towards high nm23 gene expression in grade 2 tumors compared with grade 1 (grade 1 vs grade 2, nm23-H1: p = 0.107, nm23-H2: p = 0.008; no grade 3 tumors in this study) and in high stage renal cancers (stage II vs stage III, nm23-H1: p = 0.023, nm23-H2: p = 0.005). From these results, we suggest that reduced nm23 mRNA levels are not associated with metastasis of either bladder or renal cancers and there may be some tissue-specific differences in the expression patterns of nm23-H1 and nm23-H2 in human cancers.     

Differential diagnosis and staging of urological tumors by magnetic resonance imaging compared with computed tomography

Magnetic resonance imaging (MRI) was performed on 49 urological tumors (11 renal cell carcinomas, 3 renal pelvic cancers, 2 renal angiomyolipomas, 1 renal leiomyosarcoma, 1 large renal cyst, 4 adrenal tumors, 11 bladder cancers, 2 bone metastasis from bladder cancer, 10 prostatic cancers, 1 prostatic sarcoma, 1 urethral cancer, 1 penile cancer and 1 perivesical granuloma) since October 1985 to September 1986. MRI was performed using a Signa (G.E.) with a 1.5T superconductive magnet and 3 images, including T1 weighted image, T2 weighted image, and proton density image, were obtained. In conclusion MRI is a noninvasive examination and gives more information than computed tomography despite its high cost. In renal cell carcinoma, the chemical shift in MRI and clear visualization of tumor thrombus enable accurate staging. Differential diagnosis from other renal mass lesions may be possible by the T2 weighted image. In adrenal disease, most of the adrenal masses can be differentiated, but in some cases it is impossible. In bladder cancer, wall invasion of tumor may be evaluated in T2 weighted image, and MRI is suitable for staging of locally advanced tumor. In prostatic cancer, visualization of periprostatic plexus and differentiation between internal and external gland may enable local staging and identification of low stage tumors.     

Uroepithelial tumors of the upper urinary tract following bladder cancer

Five hundred and nineteen patients with primary bladder cancer were treated between January, 1969 and December, 1984, 12 of whom had developed upper urothelial tumors. These patients had received various transurethral treatment for the primary bladder lesions, except for one patient who had undergone total cystectomy and ileal conduit diversion. Overall incidence of patients with upper urinary tract tumors following bladder cancer was 2.3%. The incidence of patients with treated bladder tumors (13.2%) for dye workers was higher than that for the general population (1.1%). The interval between initial treatment of the bladder tumor and diagnosis of the upper tract tumor ranged from 7 to 170 months (mean 70 months). The incidence of upper tract tumors increased with the passage of time. We conclude that the occurrence of upper urinary tract tumors following primary bladder cancers is promoted by nonspecific chemical irritants against the urothelium already made unstable by certain urinary chemical carcinogens.     

Clinical observation on renal pelvic and ureteral tumors

During the 18 years from October, 1971 to September, 1989, 40 patients with renal pelvic and ureteral tumors were treated at our Department of Urology. Thirty were male and 10 female, and were between 44 and 83 years old with a mean age of 65.5 years. Histopathologically, there were 38 transitional cell carcinomas and 2 squamous cell carcinomas. There was a positive correlation between grade and stage of tumor. Among the patients with transitional cell carcinoma, the five-year survival rate was 54.4% for all the patients, 57.1% for patients with renal pelvic tumors and 48.4% for those with ureteral tumors respectively, as measured by the Kaplan-Meier's method. Stage and intravascular invasion of the tumor were the most influential factors for prognosis. There was no evidence in this series to show the usefulness of postoperative adjuvant chemotherapy, such as bladder instillation or peroral administration of various anti-tumor drugs, as a prophylactic use for recurrence of the bladder tumor in low stage cases.     

Long-term follow-up of ureteral stump tumors after nephrectomy for benign renal disease

OBJECTIVE: The occurrence of primary carcinoma of the ureteral stump after nephrectomy is rare. In this study, we evaluated the clinical characteristics of ureteral stump tumors after nephrectomy for benign renal disease. METHODS: During a 16-year period, 318 consecutive patients underwent simple nephrectomy for benign renal disease (216 cases) or for donation (102 cases). Eight of these 318 patients diagnosed as having an ureteral stump tumor were treated by ipsilateral ureterectomy with cuff excision of the bladder. Pathologic findings, tumor stages, and clinical characteristics were analyzed. RESULTS: The eight ureteral stump tumors comprised; 6 transitional cell carcinomas (TCCs) and 2 squamous cell carcinomas (SCCs). The mean interval between nephrectomy and ureteral stump tumor diagnosis was 76.5 months. Six of the 8 patients had pyonephrosis and two renal tuberculosis as original renal diseases. Four of the 6 TCCs were stage T1 and 2 stage T2. There was no concomitant bladder tumor at stump tumor diagnosis. Hematuria was the major presenting symptom in 3 of the 8 patients and 4 patients were diagnosed by follow-up imaging study. Two of the 6 ureteral stump TCC patients developed bladder TCC during follow-up. The 5-year survival rate of patients with ureteral stump tumor was 37.5%. T1G1 TCC was associated with a better survival than T2 or G2 TCC. No ureteral stump tumor occurred in cases of donor nephrectomy. CONCLUSION: This study demonstrate, that long-term closed observation is needed to detect ureteral stump tumor, particularly in patients that have undergo nephrectomy for a long-standing inflammatory renal disease such as pyonephrosis or tuberculosis. Hematuria is a major presenting symptom of ureteral stump tumor. However, a follow-up imaging study is also important for ureteral stump tumor detection. The prognosis is poor in cases developing ureteral stump SCC, bladder tumor recurrence, or a high-grade ureteral tumor.     

Clinical study of urothelial tumors of the upper urinary tract. 1: Primary renal pelvic tumors

Forty primary renal pelvic tumors treated at our University between 1963 and 1981, were reviewed retrospectively. The conclusions of this study are as follows. Sex and age distribution of the patients were 30 males and 10 females (3: 1), and average age was 60.5 years old. The major symptoms were hematuria and flank pain; however, palpable mass was rare. The majority of patients were admitted to our clinic within 6 months from manifestation of symptoms. The major findings of IVP were non-functioning kidney and filling defect. The positive rate of urinary cytology was 46.7%. Total nephroureterectomy with bladder cuff was performed in 20 out of 32 cases. Histologically, 29 cases were transitional cell carcinoma and 4 cases were squamous cell carcinoma with renal calculi. Simultaneous urothelial tumors were seen in 10 cases, 3 in the ureter and 7 in the bladder. A subsequent ureteral tumor was found in one out of 12 cases in which ureters were resected incompletely, and 7 subsequent bladder tumors were found out of 32 cases receiving surgical treatment in the follow-up period. The 5-year survival rate by the actuarial method was 75.9%. Among several factors, grade and stage of the tumor were the most influencing factors for prognosis. An effective method of post-operative treatment could not be established.     

Growth of a spontaneous canine prostatic adenocarcinoma in vivo and in vitro: isolation and characterization of a neoplastic prostatic epithelial cell line, CPA 1

Neoplastic epithelium derived from a spontaneous canine prostatic adenocarcinoma has been maintained and grown in cell culture and as xenografts in athymic mice. An epithelial cell line (CPA 1) has been isolated from primary cultures and has been partially characterized in vitro. The growth of this cell line was not modified by either androgens or estrogens, and high-affinity receptors for these steroids could not be demonstrated in these cells. Xenografts were serially transplantable, with growth being similar in both sexes. Receptors for androgens and estrogens could not be detected in homogenates of xenografts or primary tumor. The histological appearances of serially transplanted tumors, and of xenografts generated by inoculation of the cell line (CPA 1) and several cloned substrains, were very similar to that of the primary tumor and were judged to be well differentiated. The characteristics of this neoplastic cell type have been compared with those of normal prostatic epithelium.     

A case of synchronous multifocal urothelial tumors in a patient with phenacetin abuse]

A 79-year-old male with phenacetin abuse was admitted to our University Hospital for treatment of asymptomatic gross hematuria. Intravenous urograpdy and computed tomography revealed synchronous right renal pelvic carcinoma and bladder carcinoma. Right nephroureterectomy and transurethral resection of bladder tumor (TUR-Bt) were performed. Histologically, right renal pelvic tumor and bladder tumor were both transitional cell carcinomas of grade 2, pT1, and grade 1 = 2, Ta, respectively. Additionally, pathological examination revealed two distal ureteral tumors, which were transitional cell carcinomas of grade 2, pTa. He also had a history of heavy tobacco-smoking (20 cigarettes per day for 50 years). We discuss the relationship between transitional cell carcinoma and phenacetin abuse as well as the influence of tobacco-smoking, and review the literature.     

Effect of various anti-cancer drugs on human renal cell carcinoma serially transplanted into nude mice

Using two xenografts of human renal cell carcinomas serially transplanted in nude mice (AM-RC-1 and AM-RC-6), both of which maintained the basic histologic features of the original tumor and showed a constant growth rate, the effects of various anticancer agents against 2 target tumors were evaluated. MitomycinC (MMC), adriamycin (ADM), cisplatinum diaminodichloride (CDDP), 5-fluorouracil (5FU), 5-fluro-2'-deoxy-beta-uridine (FUDR) and human lymphoblastoid interferon (HLBI) against AM-RC-1, and MMC, ADM, CDDP, vinblastin (VBL) and etoposide (VP-16) against AM-RC-6. Drugs other than HLBI were administered 3 times in total every three to five days by intraperitoneal injection according to Battelle Columbus Laboratories Protocol and HLBI was injected daily for 10 days intraperitoneally. Anti-cancer effects were evaluated based on tumor growth curve and changes of histologic findings. In terms of tumor growth only MMC (in a dose of 3 mg/kg) revealed a statistically significant inhibitory effect against both AM-RC-1 and AM-RC-6 (respectively P less than 0.001 and P less than 0.05). Concerning AM-RC-1, a significant difference (P less than 0.01) was recognized in the ADM group (5 mg/kg) at the time of the second administration, but evaluation could not ultimately be done owing to appearance of acute toxity after the last dose. The most remarkable histologic changes by light microscopy were recognized in the MMC group (in a dose of 3 mg/kg) against AM-RC-1. They were degenerative findings such as intracellular and nuclear vacuolation, karyorrhexis, karyolysis, karyopyknosis and marginal hyperchromatosis, which corresponded to grade IIa of the classification of the National Cancer Center. The other drugs administered to AM-RC-1 exhibited only grade O to grade I changes. On the other hand, in AM-RC-6, histologic changes were mild (less than grade II) for all the drugs. Electron microscopic features were as follows. AM-RC-1: Marked increase of vacuole of organella was observed and lumens were filled with a large quantity of debris in MMC group (3 mg/kg). In the ADM group (5 mg/kg) there was debris in lumens, although almost no changes of organella were seen. CDDP groups (both 5.6 mg/kg and 2.8 mg/kg) showed autophagic vacuole in the cytoplasm and increased collagen fibers in the stroma but little changes of organella. AM-RC-6: Mild intracellular vacuolation was recognized in the MMC group (3 mg/kg). Watery degeneration and microfibrils were found in the cytoplasm in both ADM (5 mg/kg) and CDDP (5.6 mg/kg, 2.8 mg/kg) groups.     

Present status and background of occupational uroepithelial tumors

The incidence of urothelial cancers in a group of 231 dyestuff plant workers who had been exposed to benzidine (BZ) or to beta-naphthylamine (BNA) was surveyed from 1962 to 1988. Fifteen out of 231 patients (6.5%) were found to have bladder cancer with the mean age at onset of 57.1 +/- 8.7 years. The estimated average period of engaging in this dyestuff exposure for these 15 patients was 92.4 +/- 47.3 months. The mean latent periods from the initial and last exposure until tumor development were 28.8 +/- 5.7 years and 16.6 +/- 7.0 years, respectively. Good negative correlation was observed between exposure periods and latent periods from the last exposure to onset (R = -0.06814). All 15 patients demonstrated tumors in the bladder, and one patient had a metachronous upper urinary tract cancer after treatment for bladder cancer. All tumors were histologically transitional cell carcinomas except for one adenocarcinoma. For initial treatment, five underwent total cystectomy, eight had transurethral resection (TUR) of the tumor, and one had partial cystectomy. Five out of 8 patients who had TUR have developed recurrent bladder tumors, and two of those patients underwent total cystectomy for second treatments. The mean follow-up period was 8.6 +/- 5.2 years, with two dying of cancer. For detection and monitoring, flow cytometric (FCM) analyses were available in five cases with bladder tumor and in two follow-up cases after bladder preserving treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous bilateral renal pelvic tumors

BACKGROUND: A 72-year-old man was admitted with gross hematuria. Investigations revealed bilateral renal pelvic tumors. METHODS/RESULTS: Via a midline incision, left nephroureterectomy with bladder cuff resection was performed for the large left-sided tumor. The right small solitary right-sided tumor was endoscopically resected simultaneously. Histologically, both tumors were grade 2 transitional cell carcinomas without muscular invasion. CONCLUSION: There has been no evidence of recurrence or metastasis 30 months postoperatively.     

同时性尿路上皮多器官肿瘤

目的探讨同时性尿路上皮多器官肿瘤的临床特点，提高诊治效果。方法对获随访的65例同时发生于多个尿路器官的尿路上皮肿瘤进行回顾性总结。男39例，女26例。年龄45～79岁，平均66岁。肾盂癌合并输尿管癌21例，输尿管癌合并膀胱癌17例，肾盂癌合并膀胱癌14例，同时合并肾盂输尿管膀胱癌13例。T1 6例，T2 35例，T3 22例，T4 2例。G1 5例，G2 32例，G3 28例。随访6个月～14年。结果术前诊断同时存在尿路上皮多器官肿瘤59例（90．8％）。术前诊断准确率B超32．3％（21／65），IVU 45．3％（29／64），逆行肾盂造影56．8％（25／44），CT 81．5％（53／65），螺旋CT尿路三维重建91．7％（11／12），CT三维重建联合膀胱镜检查100．0％（12／12）。术后再发膀胱癌46例（70．8％），2年内再发36例。G1、G2、G3术后膀胱癌再发率分别为20．0％、81．3％和67．9％，G1与G2～G3两组比较差异有统计学意义（P＜0．05）。T1、T2、T3术后膀胱癌再发率分别为66．7％、80．0％和63．6％；T4 2例均于术后短期内死亡，无膀胱癌再发。术后即时膀胱灌注化疗术后膀胱癌再发率63．2％（12／19），未灌注化疗者73．9％（34／46）。3年生存率41．7％，5年生存率30，6％。结论螺旋CT三维成像加膀胱镜检查是发现同时性尿路上皮多器官肿瘤的良好方法。同时性尿路上皮多器官肿瘤术后容易再发膀胱癌，肿瘤细胞分化不良者术后膀胱癌的再发率高。术后密切观察，建议除定期膀胱镜检查外，尚需行尿路造影检查。     

Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance

We measured the levels of messenger RNA of the human multidrug-resistance gene (MDR1) in 25 urogenital tumors before chemotherapy. Many of the renal cell carcinomas continued to express MDR1 gene at high levels, reflecting the increased expression of MDR1 RNA in normal kidneys. In other urogenital tumors, the MDR1 RNA levels were low reflecting low MDR1 RNA levels in normal bladder, prostate and testis. For comparative purposes, we performed in vitro chemosensitivity testing on many tumor samples using soft agar culture techniques. Vinblastine sensitivity in vitro inversely correlated with MDR1 RNA levels (p less than 0.01). Moreover, mean sensitivity of seven renal cell carcinomas to vinblastin was significantly lower than that of the other seven cancers (p less than 0.05). As for doxorubicin, mean sensitivity of six renal cell carcinomas was lower than the others (p less than 0.1). These results suggest that the high MDR1 RNA levels in renal cell carcinomas are associated with intrinsic multidrug-resistance.     

Histochemical studies of bladder tumors

Twenty seven bladder tumors, three ureteral tumors and one renal pelvic tumor were studied by means of light microscopic histochemical methods for demonstration and identification of acid mucopolysaccharides. Alcian blue (pH 1.0), alcian blue (pH 2.5), periodic acid-Schiff (PAS) and aldehyde-fuchusin stainings were performed. These stainings showed that all tumor specimens contained acid mucopolysaccharides. For identifying individual acid mucopolysaccharides, enzyme digestion procedures were performed prior to staining with alcian blue. (streptomyces hyaluronidase, testicular hyaluronidase, chondroitinase ABC, chondroitinase AC, keratanase, heparinase, heparitinase.) According to these experiments, high-grade, and high-stage tumors contained large amounts of sulfated mucopolysaccharides. Squamous cell carcinomas of the bladder contained especially large amounts of chondroitin sulfate AC.     

Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma.

Primary adenocarcinoma of the urinary bladder sometimes causes a diagnostic dilemma because it can be indistinguishable morphologically from adenocarcinoma of colorectal origin secondarily involving the bladder by metastasis or direct extension. It is much less well studied than conventional urothelial carcinoma and colorectal adenocarcinoma because of its rarity. The current study was specifically designed to investigate whether an important mechanism involved in the pathogenesis of colorectal adenocarcinoma, beta-catenin dysregulation, was also important for the development of primary bladder adenocarcinoma and whether these two morphologically similar tumors could be distinguished immunohistochemically. Formalin-fixed, paraffin-embedded tissues from 17 primary adenocarcinomas of the urinary bladder, 16 colorectal adenocarcinomas involving the bladder, and 10 conventional urothelial (transitional) carcinomas were included in this study. Thirteen of the primary bladder adenocarcinomas were moderately to well differentiated (enteric type) and morphologically indistinguishable from colorectal cancers. The remaining four primary tumors were poorly differentiated (two cases) or of clear cell type (two cases). Immunohistochemical studies using a panel of monoclonal antibodies demonstrated positive nuclear staining for beta-catenin expression in 13 of the 16 (81%) colorectal adenocarcinomas secondarily involving the bladder but in none of the primary adenocarcinomas or the urothelial carcinomas. Instead, positive membranous (and some cytoplasmic) staining was present in all primary bladder tumors with the exception of two poorly differentiated adenocarcinomas where no beta-catenin staining was detected. All secondary colorectal adenocarcinomas stained negatively for CK7 and thrombomodulin (TM), whereas positivity for CK20 was observed in 15 (94%) cases. All urothelial carcinomas stained positively for CK7 and TM, and four of them also for CK20. Primary adenocarcinomas of the bladder showed mixed staining patterns for CK7, CK20, and TM with a positive rate of 65%, 53%, and 59%, respectively. These data indicate that dysregulation of beta-catenin, an important aberration seen in colorectal carcinogenesis, does not appear to play a role in the pathogenesis of the bladder adenocarcinoma. In addition, our data demonstrate that a panel of immunostains, including CK7, CK20, TM, and beta-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.     

Limitations of size as a criterion in the evaluation of adrenal tumors

BACKGROUND: Size has been considered to be the single best predictor of malignancy in adrenal neoplasms that have been identified incidentally. However, small adrenal cortical cancers have been reported from multiple centers. METHODS: We retrospectively evaluated the value of tumor size and other clinical parameters in the prediction of the presence of adrenal malignancy. RESULTS: The records of 117 patients who underwent evaluation for tumors of the adrenal gland were reviewed. The median tumor size of the adrenal cortical carcinomas (n = 38 carcinomas) was 9.2 cm (range, 1.7-30 cm); 5 cancers (13.5%) were smaller than 5.0 cm. The median overall size of the benign tumors, excluding pheochromocytomas, was 4.0 cm (n = 38 carcinomas); 10 benign tumors (26%) were larger than 5.0 cm. The imaging features of 4 of 5 small adrenal cancers predicted malignancy; the remaining patients had hormonally functioning tumors. The imaging features of 7 of 10 large benign adrenal tumors predicted benign histologic features, including 5 of 5 myelolipomas. CONCLUSIONS: Although size remains a good predictor of the histologic features and clinical behavior of adrenal neoplasms, both small adrenal cortical cancers and large benign tumors occur with measurable frequency. High-quality imaging studies may be helpful in the identification of relatively small adrenal cancers and of characteristic benign lesions that may be selectively followed.     

Differentiation of primary and metastatic clear cell tumors in the liver by in situ hybridization for albumin messenger RNA

Clear cell neoplasms presenting as metastatic hepatic masses may be difficult to differentiate histologically and immunohistochemically from hepatocellular carcinoma (HCC) with prominent clear cell features, especially in small biopsy specimens. In situ hybridization (ISH) for albumin messenger RNA (mRNA) has been previously shown to be sensitive and specific for the detection of hepatocellular differentiation, but its use for the identification of clear cell HCC has not been previously evaluated. Among 309 cases of hepatocellular carcinoma diagnosed at Mayo Clinic between 1985 and 1998, 30 cases (9.7%) with at least 30% (range, 30%-90%; median 60%) clear cells were studied by ISH for albumin mRNA. In addition, immunohistochemical expression of AFP and polyclonal CEA, serum determination of AFP, and histopathologic analyses of the tumor were done. Forty-two clear cell tumors were used as a control group: 21 metastatic clear cell tumors to the liver (14 renal cell carcinomas and 7 adrenal cortical carcinomas) and 21 primary clear cell tumors of the retroperitoneum (10 renal cell carcinomas, 5 adrenal cortical adenomas, 4 adrenal cortical carcinomas, and 2 ovarian carcinomas). ISH for albumin mRNA was reactive in 28 of 30 cases of clear cell HCC (93%). Clear cell HCC expressed AFP (15 cases; 50%) and polyclonal CEA (19 cases; 63%). Tumors expressed either AFP or polyclonal CEA in 23 cases (77%). Elevated serum AFP was present in 24 of 26 cases (92%). These results indicate that ISH for albumin mRNA is a useful method to distinguish clear cell HCC from other clear cell carcinomas metastatic to the liver and clear cell neoplasms in the retroperitoneum.