Oncoprotein changes in the flat lesions with atypia and invasive neoplasms of the urinary bladder.

We analyzed six cystectomized specimens diagnosed as transitional cell carcinoma by immunohistochemical evaluation to determine the presence of c-erbB2, transforming growth factor-alpha (TGF-alpha), c-myc, c-fos, and c-fms. Representative sections of flat lesions with atypia (e.g., reactive atypia, dysplasia, and carcinoma in situ) and invasive neoplasms (transitional cell carcinoma, TCC) were selected for each cystectomy specimen according to the new WHO/ISUP classification. The average percentage of cells found positive for c-erbB2 were 16.3%, 45.5%, 46.1% and 67.7% in the reactive atypia, dysplasia, carcinoma in situ, and invasive TCC, respectively. The average percentage of cells found positive for TGF-alpha were 9.7%, 13.3%, 13.5%, 30.3%, respectively. The cells were negative for the oncoproteins c-myc and c-fos. The average percentage of cells found positive for the oncoprotein c-fms was 10.6%, 15.5%, 16.7%, and 45.5% respectively. The results of this study indicated that various oncoproteins are expressed differently. c-erbB2, TGF-alpha and c-fms expression was gradually increased during tumorous progression of the urothelium from reactive atypia to invasive carcinoma. The presence of c-erbB2, TGF-alpha and c-fms is an important marker for detection of an early precursor lesions of invasive carcinoma. However, c-myc and c-fos were not expressed in the urothelial reactive atypia and dysplasia and did not correlate with tumor progression.

Drug concentration-dependent expression of multidrug resistance-associated protein and P-glycoprotein in the doxorubicin-resistant acute myelogenous leukemia sublines.

The multidrug resistance of cancer cells can be mediated by an overexpression of the human MDR1 and MRP genes, which encode the transmembrane efflux pumps, the 170 kDa P-glycoprotein (Pgp) and the 190 kDa multidrug resistance-associated protein (MRP), respectively. In this study, we investigate which protein is preferentially overexpressed in the function of doxorubicin concentrations in the acute myelogenous leukemia cell line (OCI/AML-2). Multidrug-resistant AML-2 sublines were isolated in doxorubicin concentrations of 20, 100, 250, and 500 ng/ml. MRP was at first expressed at low concentrations of less than 5 x IC50 (100 ng/ml) of doxorubicin followed by the overexpression of Pgp with concentrations of more than 12.5 x IC50 (250 ng/ml) of doxorubicin. In addition, it appeared that increased amounts of MRP and its mRNA in AML-2/DX20 and /DX100 decreased gradually in both AML-2/DX250 and /DX500 overexpressing Pgp. In conclusion, it is thought that the overexpression of MRP or Pgp is dependent upon drug concentrations. It could be implicated that the overexpression of MRP might be negatively related to that of Pgp.

Metastatic renal cell carcinoma to the bladder: a clinicopathologic and immunohistochemical study.

Although rare, renal cell carcinoma (RCC) can metastasize to the bladder. When this occurs, it might complicate diagnosis. Morphologically, RCC can be confused with transitional cell carcinomas (TCCs), especially those exhibiting clear cell features, and also with other bladder tumors, such as paragangliomas and metastatic melanomas. We report seven cases of RCC metastatic to the bladder that occurred in 6 men and 1 woman who were 35 to 69 years old. The most common presenting symptom was the reappearance of hematuria, which developed from 2 to 131 months (mean, 41.3 mo) after the removal of the primary RCC. In all of the patients, the metastatic RCC involved multiple organs; no case had an isolated metastasis to the bladder. The prognosis was poor, and five patients died of disease between 4 and 24 months (mean, 12.8 mo) after diagnosis of the metastasis to the bladder. The remaining two patients were lost to follow-up. All of the tumors were conventional clear or "granular" cell RCCs, with nuclear grades of 2 or 3. In five patients, metastases were confined to the lamina propria, but in two patients, tumors involved the muscularis propria as well. A comparative immunohistochemical study showed that metastatic RCCs were positive for CAM5.2, vimentin, and Leu-M1, and negative for cytokeratin 20, cytokeratin 7, 34betaE12, carcinoembryonic antigen, S-100 protein, HMB45, and chromogranin. Classic and clear cell TCCs were positive for all of the cytokeratins and carcinoembryonic antigen and negative for vimentin. Paragangliomas were positive for chromogranin and showed scattered positivity for the S-100 protein in the sustentacular cells. Metastatic melanomas were positive for S-100 protein and HMB45. The histologic appearance of RCC, particularly the delicate fibrovascular stroma with abundant sinusoidal vessels, is a feature that can be used to recognize the tumor. When there is difficulty diagnosing metastatic RCC, TCC, or other tumors in the bladder, the immunohistochemical findings can assist in the differential diagnosis.

Giant hidradenocarcinoma: a report of malignant transformation from nodular hidradenoma.

A giant hidradenocarcinoma presented by a 75-year-old female is reported. The patient had a malignant transformation within a nodular hidradenoma involving the right postauricular area, which was treated by mass removal and a right radical neck dissection with a free-flap covering. Malignant hidradenocarcinoma is the least common adnexal tumor of uncertain origin. They are usually malignant from their inception, but some develop from a benign counterpart. To the authors' knowledge, only three cases have been reported previously. Two histologically distinct components were seen in this tumor: (i) typical nodular hidradenoma, which constituted a small part of the tumor; and (ii) carcinoma with areas of transition. The secretory cells of hidradenocarcinoma showed decapitation secretion on light and electron microscopic observations, which is evidence of apocrine differentiation. Histologically, this case was concluded as a hidradenocarcinoma arising from a long-standing nodular hidradenoma. A literature review is presented and the histological, immunohistochemical and ultrastructural features are described.

Malignant mixed Müllerian tumor (homologous type) of the adnexa with neuroendocrine differentiation: a case report.

Malignant mixed müllerian tumors (MMMT) are unusual neoplasms occurring mostly in the uterus. In the ovary, they are very rare and represent fewer than 1% of all ovarian malignancies; in the salpinx, they are even rarer than those of the ovary. We report a carcinosarcoma of the left adnexa having features of neuroendocrine differentiation in a 69-year-old female. The tumor contained both adenocarcinoma and squamous cell carcinoma having dear cell change admixed with an undifferentiated malignant mesenchymal component. The sarcoma components consisted of spindle cells, small-round cells and bizarre giant cells mimicking rhabdomyoblast. Almost all of the carcinomatous glandular components and some foci of the squamous cell and undifferentiated carcinomatous components were focal positive for S-100 protein, chromogranin, neuron specific enolase, synaptophysin and Leu-7. Electron microscopy revealed membrane-bound neurosecretory granules in the cytoplasm of some glandular epithelial cells. Histologically, the tumor involved the left adnexa, abdominal peritoneum, surface of the bladder dome, omentum and left external iliac lymph node (stage IIIc).

Spermatic cord contamination in testicular cancer.

It is not uncommon to find testicular germ-cell tumors in the spermatic cord. This may represent contamination or true involvement (vascular invasion or direct tumoral extension into the cord). A correct identification of the process has important clinical implications. In a review of 326 testicular germ-cell tumors, 79 (24.2%) revealed tumor in the spermatic cord. Of these 79, contamination was found in 57 (72.1%), true involvement in 15 (19%), and true involvement and contamination in 7 (8.9%). Spermatic cord contamination was seen most frequently with seminomas: 34 (24.1%) of 141 seminomas and 20 (15.4%) of 130 mixed germ-cell tumors. Eighteen of the 20 mixed germ-cell tumors contained an embryonal carcinoma component. True involvement was seen most frequently in embryonal carcinoma. Six (15.4%) of 39 pure embryonal carcinomas demonstrated true cord involvement. Six mixed germ-cell tumors with true cord involvement contained an embryonal carcinoma component. Distinguishing between true involvement of the spermatic cord and contamination can occasionally be problematic. Because true involvement, especially at the spermatic cord resection margin, identifies patients at a high risk for relapse, the problem of contamination caused by inadequate precautionary measures can be avoided by meticulous handling and processing of the specimens.