Elevated expression of the retinoic acid-metabolizing enzyme CYP26C1 in primary breast carcinomas.

Retinoic acid (RA)-metabolizing enzyme CYP26A1 has been shown to have increased expression levels in breast cancers and to effectively promote the survival of breast carcinoma cells, implying a potential oncogenic function. However, the expression of CYP26C1, another CYP26 family member, in primary breast carcinoma remains to be clarified. In the present study, we examined the expression of CYP26C1 by immunohistochemistry, using three different types of microarray, and observed strong cytoplasmic staining of CYP26C1 in 73 of the 219 (33.3 %) breast carcinomas. In contrast, CYP26C1 was not expressed in normal ductal and lobular cells in non-neoplastic tissue. Interestingly, increased expression of CYP26C1 was significantly associated with a high Ki-67 labeling index and a grade of tumor. However, CYP26C1 immunoreactivity was not associated with clinicopathological variables, including primary tumor status, lymph node involvement, distant metastasis, and tumor stage. In addition, CYP26C1 positivity was independent of the expression status of the hormone receptors and immunohistochemical surrogates for the intrinsic subtypes of breast cancer. This report is the first to demonstrate elevated expression of CYP26C1 in primary breast carcinomas. Based on the RA-catabolizing activity of CYP26C1, our data suggest that CYP26C1 expression may contribute to neoplasia in the breast.

Investigation of aluminum and iron deposition on metaplastic bones in three patients with diffuse pulmonary ossification.

Diffuse pulmonary ossification (DPO) is a rare pulmonary lesion. DPO is typically detected at autopsy rather than premortem. Recently, however, several cases were diagnosed antemortem using computed tomography, high-resolution computed tomography, or video-assisted thoracic surgery. In the present study, we evaluated DPO at autopsy from two patients with post-myocardial infarction (cases 1 and 3) and one patient with duodenal cancer (case 2). Multiple metaplastic bones (nodular in case 1 and 3 or dendriform in case 2) were detected in these three cases. In an attempt to detect aluminum and iron deposition in these metaplastic bones, histochemical investigations were performed. The two nodular types of one and three cases were positive for aluminum and iron, but the dendriform type of case 2 was positive only for aluminum. The depositions occurred in a linear pattern along the calcifying front. It is of great interest that these deposition patterns were similar to those of bones from three previously reported DPO cases and from the bones of hemodialysis patients. It is suggested that these abnormal metal depositions in the calcifying front might disturb the normal mineralization processes of the metaplastic bones, although no morphological abnormality was detected, except for dense black color of calcifying front lines. Further investigations are needed in more patients with DPO to obtain more information on this topic.

Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia of the pancreas, including carcinoma, dysplasia, and hyperplasia.

KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study.

Immunohistochemical analysis of invasive micropapillary carcinoma pattern in four cases of gastric cancer.

Gastric cancer with the invasive micropapillary carcinoma (IMPC) pattern has been reported to be a variant with poor prognosis and rapid progression. To the best of our knowledge, only 4 cases of gastric cancer from Japan and 11 cases from Korea have been reported to contain the IMPC pattern. In the present study, 4 cases of gastric cancer containing the IMPC pattern from 2 Japanese men and 2 Japanese women are reported. The cancer tissues, including a recurrent lesion in 1 case and lymph node metastases in 2 other cases, were examined immunohistochemically to identify suitable markers for demonstrating the peculiar "inside out" pattern of IMPC and for analyzing HER2 expression. A characteristic IMPC pattern occupied more than 10% of each cancer tissue in these 4 cases. Lymphatic invasions were very often detected; in fact, lymph node metastases were detected in 3 out of 4 cases. The unique "inside out" pattern in IMPC was clearly revealed in all cases by staining with antibodies to both epithelial membrane antigen (EMA) and KL-6, but not with an antibody to CD10. HER2 was positive in 3 of 4 cases with the IMPC pattern, including cases with a recurrent lesion or lymph node metastases. Fluorescence in situ hybridization (FISH) analyses disclosed positive results in case 1, and case 3 including lymph node metastatic foci. Highest FISH titer was 6.8 in case 1, revealing marked amplification of HER-2 gene. Four cases of gastric cancer with the IMPC pattern were reported. EMA and KL-6, but not CD10, were particularly useful markers for visualizing the characteristic "inside out" pattern of the IMPC pattern in stomach cancers, similar to the markers for breast and urinary bladder cancers.

Composite paraganglioma and ganglioneuroma in the retroperitoneum: a case report.

Reports of a composite paraganglioma (PG) and ganglioneuroma (GN) in the retroperitoneum are rare. In the present case, dynamic computed tomographic (CT) findings showed a 30 × 22 × 20 mm tumor that was located in the retroperitoneum and which was dissociated from pancreatic tissue and the left adrenal gland. The markedly reddish tumor showed a clear margin and central multicystic changes on the cut surface. The tumor was composed of two major components, the PG and the GN. The paraganglionic cells in the PG component, which were arranged in a nested pattern, occupied the main and central part of the tumor. Both ganglionic cells and Schwann cells in the GN were located in a unorganized pattern in the periphery. The paraganglionic cells exhibited a Zellballen pattern, which consisted of an association of edematous vascular-rich stroma and focal hemorrhage, resulting in multicystic changes. These centrally located tumor cells were pleomorphic in part and did not have mitotic figures. In the periphery, Schwann cells, which were arranged in an obscure and fascicular pattern that was intermingled with large ganglionic cells, were located adjacent to the PG component with a mostly sharp margin. With higher magnification, the border was not as sharp, as revealed especially with chromogranin-A immunostain, in which both the PG and GN components were focally intermingled with each other. The histogenesis of the composite PG and GN was thought to be extraadrenal neural crest cells in the retroperitoneum because the tumor was not located in the adrenal gland or the Zuckerkandl organ, according to the CT findings. The immunohistochemical findings of this rare case of a composite PG and GN in the retroperitoneum are reported with a focus on the peculiar arrangement of these two components.

Marked infiltration of eosinophils in necrotizing granulomas in the resected hepatic bed after cholecystectomy resulting from gallbladder cancer and metastatic liver cancer is associated with peculiar peripheral eosinophilia.

It is known that after transurethral resection of the prostate (TUR-P) or a bladder tumor (TUR-BT), necrotizing granuloma formation associated with massive eosinophil accumulation can be detected at the site of the scar, revealing marked eosinophilia. This condition is called post-TUR prostatitis or cystitis. In the present study, we noticed a similar phenomenon in five patients who underwent cholecystectomy, of whom four had gallbladder adenocarcinoma and one had metastatic liver cancer originating from the rectum. We detected necrotizing granulomas with massive eosinophil accumulation, associated with marked eosinophilia. To induce these phenomena, the interval between the first operation (i.e., cholecystectomy) and the second operation (i.e., resection of the hepatic bed and extrahepatic bile duct) is very important. If the interval was 1 week, no granuloma formation was detected. On the other hand, if it was more than 2 weeks, the resected hepatic bed contained necrotizing granulomas with substantial eosinophil accumulation combined with an increase in peripheral eosinophilia (up to 34% in one case). Secondary resection was necessary to induce eosinophilia after cholecystectomy. In this sense, malignancies possessed a relationship with delayed eosinophilia. In the granulomas, some foreign body-type multinucleated giant cells were positive for both anti-interleukin (IL)-5 and CD68 antibodies. In sharp contrast, no eosinophilia was detected after cholecystectomy, with or without hepatic resection consequent to severe adhesion. Clinicians as well as pathologists should keep in mind that these peculiar phenomena of eosinophil accumulation surrounding the necrotizing granulomas and peripheral eosinophilia after cholecystectomy could occur.

Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer.

Tobacco smoke influences cancer development in tissues that are not directly exposed, and epidemiological studies have indicated that smoking women might experience decreased risk of breast cancer as a result of antiestrogenic effects. However, it remains to be clarified whether nicotine, one of the major addictive and best-investigated constituents of tobacco smoke, has any effect on breast cancer. Our recent work demonstrated that the retinoic acid metabolizing enzyme CYP26A1 enhances oncogenic and cell survival properties of breast carcinoma cells, implying a role as an oncogene. Here, we present evidence that nicotine significantly suppresses constitutive expression of CYP26A1, and that cells treated with nicotine exhibit enhanced sensitivity to apoptosis. In addition, nicotine may inhibit anchorage independent growth, cellular invasiveness and motility. These data show that nicotine can limit CYP26A1-mediated oncogenic characteristics, and suggest mechanisms by which nicotine might inhibit breast cancer development.

Fascin-1 expression correlates with repression of E-cadherin expression in hepatocellular carcinoma cells and augments their invasiveness in combination with matrix metalloproteinases.

Expression of fascin-1, an actin bundling protein, is a poor prognostic factor in hepatocellular carcinoma (HCC). However, its biological role in HCC cells remains unclear. Using human HCC tissues and cell lines HLE, Hep3B, and Huh7, we investigated whether fascin-1 is involved in epithelial-mesenchymal transition (EMT) and increases invasiveness, thus serving as a promoter of cancer aggressiveness. Immunohistochemical analysis revealed that fascin-1 expression in 19% of primary HCCs was associated with repression of E-cadherin expression, indicating EMT. In vitro, HLE cells showed high fascin-1 expression, loss of E-cadherin, and efficient invasion through Matrigel. Knockdown of fascin-1 significantly repressed invasiveness of the HLE cells and slightly induced E-cadherin expression. In contrast, Huh7 cells had low fascin-1 levels, high E-cadherin expression, and were expectedly non-invasive. However, forced overexpression of fascin-1 conferred only modest invasiveness without E-cadherin repression, indicating that fascin-1 alone cannot effectively stimulate invasiveness or EMT. Furthermore, Hep3B cells were non-invasive despite high fascin-1 expression. Nevertheless, fascin-1 overexpression dramatically increased the migratory potential of Huh7 cells. We then evaluated matrix metalloproteinases (MMPs) 2 and 9 from the HCC cell lines. Significant MMP secretion was only found in HLE cells. Although MMP levels were not elevated in fascin-1-overexpressing Huh7 cells, their invasiveness was remarkably augmented by coculture with HLE cells, and was suppressed in the presence of an MMP inhibitor. In conclusion, we propose that fascin-1 primarily acts as a migration factor associated with EMT in HCC cells and facilitates their invasiveness in combination with MMPs.

Combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus.

Hepatoid adenocarcinoma arising in the esophagus is extremely rare. To date, there are only 3 cases in the world English literature. We report the fourth case here. A 76-year-old Japanese man was admitted to our hospital because of the deterioration of nephritic syndrome. He presented with chest burn, and the endoscopic examination of upper digestive tract disclosed the tumor in the lower esophagus. The subtotal esophagectomy was undertaken because of esophageal cancer. The postoperative histologic examination showed the finding of combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus. Immunohistochemically, hepatoid adenocarcinoma cells were positive for a-fetoprotein, hepatocyte, a1-antitrypsin, a1-antichymotrypsin, and CDX2, but negative for MUC5AC and MUC6. Esophageal hepatoid adenocarcinoma seems to be closely associated with Barrett esophagus and show the intestinal phenotype rather than gastric phenotype.

Familial gastrointestinal stromal tumor with germ line mutation of the juxtamembrane domain of the KIT gene observed in relatively young women.

Familial gastrointestinal stromal tumor (GIST) is an extremely rare autosomal dominant disorder, and approximately 20 families have been reported to date. In this article, we present one additional family. A 25-year-old Japanese woman presented with abdominal pain, and subsequent image analyses disclosed multiple tumors measuring 12 cm in maximum diameter in the lower digestive tract. The postoperative histologic examination showed multiple GISTs and diffuse hyperplasia of interstitial cells of Cajal. Her mother had a history of GIST in the digestive tract. Three members of this family including her younger sister and mother had cutaneous hyperpigmentation of external genitalia and axilla. Their DNA samples showed identical missense mutation at exon 11 in the juxtamembrane domain of the KIT gene, and this mutation site was considered to be a hot spot in familial GIST. One year after, her younger sister suffered from multiple GISTs in the digestive tract at the age of 25 years. To correctly diagnose familial GIST, mutual information should be exchanged among clinicians, pathologists, and molecular scientists.

Clear cell renal cell carcinoma with focal renal angiomyoadenomatous tumor-like area.

Recently, renal angiomyoadenomatous tumor (RAT) has been identified. However, there are no descriptions about clear cell renal cell carcinoma (RCC) with focal RAT-like features. A 33-year-old Japanese man was found to have a tumor in the left kidney. Macroscopically, the tumor extended into the perinephric fat tissue, and the cut surface showed the yellowish color. The histologic examination of the tumor consisted of 2 components of clear cell RCC and RAT-like area. The RAT-like area showed the admixture of epithelial cells with basophilic or clear cytoplasm and stromal component containing leiomyomatous stroma, fine capillary network, and pericytic network. Immunohistochemically, epithelial neoplastic cells in RAT-like area were diffusely positive for CD10 and RCC Ma. G-band karyotype showed the structural abnormality of chromosome 3 and both components of clear cell RCC and RAT-like area revealed the identical VHL gene mutation. Finally, pathologists should pay attention to the presence of clear cell RCC focally resembling RAT.

High-grade mucinous tubular and spindle cell carcinoma: comparative genomic hybridization study.

Mucinous tubular and spindle cell carcinoma (MTSCC) has recently been integrated into the World Health Organization classification. Although MTSCC is generally a low-grade carcinoma, MTSCC with high-grade morphology has been recently reported. We present the first case of high-grade MTSCC with comparative genomic hybridization findings. A 60-year-old Japanese man presented with weight loss and general fatigue. He underwent radical nephrectomy because of the clinical diagnosis of renal cancer. Histologic examination of renal tumor showed findings of high-grade MTSCC. Comparative genomic hybridization analysis showed gain of chromosomes 1q, 7, 16, 19q, and Y and loss of chromosomes 1p, 6p, 8p, 11q (del(11)(q23)), and 13. G-band karyotype showed gain of chromosomes 2, 3, 5, 7, 12, 16, and 20 and loss of chromosome 15. Results of our molecular genetic analysis support the idea that high-grade MTSCC is a real counterpart of low-grade MTSCC. There is no evidence to designate such tumors as unclassified renal cell carcinoma.

Acquired cystic disease-associated renal cell carcinoma with sarcomatoid change and rhabdoid features.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently described entity. To the best of our knowledge, there are no reports of ACD-associated RCC with sarcomatoid and rhabdoid changes. In this article, we present the first case of such a tumor. A 56-year-old Japanese man has received long-term hemodialysis and had a history of right renal cancer. Following the discovery of metastatic cancer in the thoracic wall, detailed imaging studies revealed a mass in the left kidney. The histologic examination of the left renal tumor showed ACD-associated RCC with sarcomatoid change and rhabdoid features. Immunohistochemically, intracytoplasmic globular inclusions in rhabdoid cells were positive for vimentin and cytokeratin CAM5.2. The G-band karyotype showed the following changes: 46, X, +X. -Y[1]/43, idem, add(2)(q31), -6, -9, -14, -15, +16, -22, +mar1[6]/46, XY[2]/abnormal cell[11]. In conclusion, pathologists and urologists should be aware that rhabdoid features may occur in ACD-associated RCC and that the loss of chromosomes 9 and 14 may occur during the process of sarcomatoid change in ACD-associated RCC.

Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin.

Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis. CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, has been shown to result in a state of functional VAD of the cell. Recently, we demonstrated that CYP26A1 efficiently promotes cell survival properties and eventually contributes to the carcinogenic process, implying roles as an oncogene. To clarify the possible association between VAD caused by CYP26A1 expression and the development of human epithelial neoplasia, we examined whether enhanced expression of CYP26A1 might be observed in various lesions of human skin. We report here that basal keratinocytes showed only weak positivity of CYP26A1 in sunlight-nonexposed areas, whereas strong positive staining was observed in skin from chronically sunexposed body areas and in epidermis that had the dysplastic changes known as actinic keratosis. However, we found no expression of constitutive CYP26A1 in skin malignancies such as squamous cell carcinomas. Our observation suggests an involvement of enhanced CYP26A1 expression causing a functional VAD state in skin that can potentially lead to neoplastic transformation of keratinocytes in an early phase during skin carcinogenesis.

Acquired cystic disease-associated renal cell carcinoma: an immunohistochemical and fluorescence in situ hybridization study.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently identified. However, there are only a few genetic studies to date. In this article, we performed an immunohistochemical and fluorescence in situ hybridization (FISH) study for six cases including one case with sarcomatoid change. As a result, we observed frequent immunohistochemical expression of AMACR. FISH of chromosome 3 showed trisomy for three cases, monosomy for two cases, and disomy for one case. Additionally, FISH of chromosome 16 showed trisomy for three cases, monosomy for two cases, and both trisomy and monosomy for one case. Furthermore, both the carcinomatous area and the sarcomatoid area of one ACD-associated RCC with sarcomatoid change revealed monosomy of chromosomes 3, 9, and 16 but showed disomy of chromosome 14. In conclusion, the numerical abnormalities of chromosomes 3 and 16, irrespective of gain or loss, may be characteristic of ACD-associated RCC.

Immunohistochemical application of S100A1 in renal oncocytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma.

S100A1 is a calcium-binding protein and a member of the S100 family. Recently, S100A1 immunohistochemistry may be an available marker in the differential diagnosis between renal oncocytoma and chromophobe renal cell carcinoma (RCC). However, there are no reports on S100A1 expression in oncocytic papillary RCC that has been recently identified. In this article, we immunohistochemically examined the expression of S100A1 protein in 18 renal tumors including 4 renal oncocytoma, 10 chromophobe RCCs, and 4 oncocytic papillary RCCs. All the cases of renal oncocytoma and oncocytic papillary RCC showed a positive reaction for S100A1 with cytoplasmic pattern. In chromophobe RCC, 3 of 4 tumors with typical variant and 4 of 6 tumors in eosinophilic variant were completely negative for S100A1. Finally, S100A1 immunohistochemistry may be useful in distinguishing renal oncocytoma from chromophobe RCC, but it may be of no use in the differential diagnosis between renal oncocytoma and oncocytic papillary RCC.

Chromophobe renal cell carcinoma with prominent lymph node metastasis and polysomy of chromosome 21: poorly differentiated form or "presarcomatoid" form?

Lymph node metastasis of chromophobe renal cell carcinoma (RCC) is extremely rare. It has been recently reported that sarcomatoid chromophobe RCC frequently show polysomy of chromosomes 1, 2, 6, 10, and 17. In this article, we report an unusual case of chromophobe RCC. A 42-year-old Japanese woman presented with hematuria and complained of inguinal pain 2 months after the initial symptoms. Radical nephrectomy and renal hilar lymphadenectomy were performed. The tumor was 8 cm in greatest diameter; its cut surface was beige in color. Large metastasis to the renal hilar lymph node was identified. Histological examination of the right renal tumor met the criteria of chromophobe RCC. In addition to histological findings of typical chromophobe RCC, small cell foci, comedo-like necrosis, trabecular growth pattern, and sclerosing stroma were observed. However, no sarcomatoid foci were identified anywhere, despite extensive tumor sampling including lymph node lesions. Immunohistochemically, neoplastic cells were positive for E-cadherin and CD117 (c-kit). Ultrastructurally, tumorous cells contained abundant mitochondria and cytoplasmic microvesicles. Fluorescence in situ hybridization showed monosomy of chromosomes 2 and 10 and polysomy of chromosome 21. Finally, we suggest that this tumor may show the poorly differentiated or presarcomatoid form of chromophobe RCC.

Re-evaluation of histological type by immunohistochemical and genetic study of transcription factors (TFE3 and TFEB) of VHL gene mutation-negative clear cell renal cell carcinoma and other special types of renal tumor.

Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Insulin-independent promotion of chemically induced hepatocellular tumor development in genetically diabetic mice.

Diabetes mellitus has been proposed as an epidemiological risk factor for human liver cancer development. One reasonable possibility is that this is attributable to hyperinsulinemia compensatory for obesity-related insulin resistance. However, diabetes mellitus is a complex disease with multiple abnormal conditions essentially caused by hyperglycemia. Therefore, it is not evident whether hyperinsulinemia is prerequisite for the elevated cancer risk. To gain a clue to answer this question, we characterized chemically induced hepatocarcinogenesis in diabetic model mice genetically deficient for insulin. Akita inbred mice originating from the C57BL/6 strain carry a heterozygous germline mutation of the insulin II gene and suffer from inherited insulin deficiency and diabetes in an autosomal dominant manner. They were mated with normal C3H/HeJ mice with high sensitivity to liver carcinogenesis and the resultant F(1) littermates, which were either normal or insulin deficient, were exposed to diethylnitrosamine and induced hepatocellular tumors were evaluated for number, size, proliferative activity, and apoptosis. Unexpectedly, both mean and total volumes of hepatocellular tumors in the insulin-deficient animals were more than twofold larger than those in the normal controls, with no significant difference in tumor number. The tumors in insulin-deficient mice showed a significantly lower frequency of apoptosis but no alteration in cell proliferation. In conclusion, our results indicate that insulin-independent liver tumor promotion occurred in diabetic mice. Clearly, insulin-independent mechanisms for the human case also deserve consideration.

Chromosomal abnormalities of clear cell renal cell carcinoma: frequent gain of chromosome 7.

Gain of chromosome 7 is well known to be a characteristic abnormality of papillary renal cell carcinoma (RCC). The purpose of the present study was to perform cytogenetic analysis of G-band karyotype in 16 clear cell RCC obtained from nephrectomy. The age of patients ranged from 50 to 79 years and the tumor size in largest dimension ranged from 1.8 to 6.2 cm. As a result, the structural abnormality of chromosome 3 was most frequently observed (eight clones). Loss of chromosome 3 and gain of chromosome 7 followed (four clones). Among four clones showing gain of chromosome 7, two were associated with the abnormality of chromosome 3 and the remaining two were devoid of the abnormalities of chromosome 3. In addition, none of all four tumors showing gain of chromosome 7 demonstrated any foci of papillary growth pattern. The present study shows that gain of chromosome 7 is not exclusive to papillary RCC, but it can be found in clear cell RCC as well, and this finding may represent a diagnostic pitfall in distinguishing clear cell RCC from papillary RCC.