Epidermal growth factor receptor (ErbB1) expression in prostate cancer progression: Correlation with androgen independence

BACKGROUND The role of the epidermal growth factor receptor (ErbB1) in the progression of prostate cancer is incompletely understood. METHODS Tissue microarrays from hormone-naive and advanced androgen-independent tumors were used to investigate the role of ErbB1 in prostate cancer progression. RESULTS ErbB1 expression in tumor tissues was strongly associated with hormone-refractory status (odds ratio = 6.67, 95% CI = (2.6, 17.4), P  = 0.0001). However, ErbB1 overexpression was not a statistically significant covariate in a multivariate proportional hazards model for biochemical failure of hormone-naÏve prostate cancer. Moreover, ErbB1 overexpression was not associated with tumor differentiation ( P  = 0.44), positive margins ( P  = 0.53), seminal vesicle invasion ( P  = 0.69), extraprostatic extension ( P  = 0.10), or preoperative PSA ( P  = 0.18) in the hormone-naÏve group. CONCLUSIONS These findings are consistent with a model in which ErbB1 expression increases during the development of the androgen-independent state, and suggest that drugs targeted toward ErbB signaling could be of therapeutic relevance in the management of advanced prostatic carcinoma. Prostate 66: 1437–1444, 2006. © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55786/1/20460_ftp.pd

Nephron-Sparing Diagnosis and Management of Renal Keratinizing Desquamative Squamous Metaplasia

Background and Purpose: Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract is a rare condition for which there is no defined management plan. A condition historically treated with extirpative surgery, conservative management would be preferable, because this is almost certainly a benign condition. We report the favorable clinical course of two cases of renal KDSM diagnosed and managed with a nephron-sparing approach, relying on ureteroscopy and serial imaging. Patients and Methods: Retrospective chart review was performed to obtain history, physical examination results, radiographic imaging, and diagnostic procedures. Results: Both patients were referred to our institution for evaluation of complex cystic renal masses. Both reported passing flaky material in their urine. Flexible ureteroscopy revealed waxy sediment in the collecting system, which broke up easily with manipulation and proved to be squamous keratin debris on cytologic and histologic examination. In 1 patient, we obtained a percutaneous needle biopsy as well, which revealed benign keratinizing squamous epithelium. All findings were consistent with KDSM. Each patient has since been followed conservatively with CT. In 1 case, there has been slight growth of the mass but no worrisome changes after 42 months. In the other case, there were several new renal collecting system filling defects on CT 17 months after diagnosis. Another ureteroscopy revealed the same findings as the original, with the addition of keratin debris draining out of the lesion into the rest of the kidney. Conclusions: Our two cases of KDSM confirm the feasibility of nephron-sparing management using a combination of diagnostic ureteroscopy and imaging surveillance. The duration of follow-up without adverse events suggests that the finding of renal KDSM is not necessarily an indication for extirpative surgery, and that conservative management is an appropriate option.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78150/1/end.2008.0501.pd

Laparoscopic and Open Surgical Nephrectomy for Xanthogranulomatous Pyelonephritis

Background and Purpose: Xanthogranulomatous pyelonephritis (XGP) is a severe, chronic renal-parenchymal infection. Nephrectomy is the treatment of choice. Because of the renal and perirenal inflammatory changes that commonly accompany XGP, the laparoscopic approach is difficult. We compared our experience with laparoscopic and open surgical nephrectomy for XGP. Patients and Methods: A retrospective chart review of all adult nephrectomy specimens with the pathologic diagnosis of XGP between January 1997 and May 2003 was performed. Preoperative presentation, operative details, and postoperative recovery and complications were included in the data collection. Results: Three patients approached laparoscopically and eight patients approached with open surgery were found to have XGP on pathologic analysis. The disease was suspected preoperatively in all patients. Among the laparoscopically treated patients, there was 1 (33%) who suffered major complications; this was the only patient who required conversion to open surgery. Among the open-surgical group, there were 2 (22%) major and 3 (33%) minor complications. Postoperative hospitalization was longer in the open-surgical group (mean 13.7 v 4.7 days), and when the case of open conversion was excluded, narcotic use was less in the laparoscopy group. Conclusions: The treatment of some XGP cases with laparoscopic nephrectomy is a possible, albeit challenging, option. The incidences of intraoperative and postoperative complications were roughly equivalent in the laparoscopic and open-surgery patients in our study. If completed, laparoscopy appears to be associated with decreased postoperative morbidity. However, this may represent selection bias, and larger, prospective studies may better define the suspected benefit.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63141/1/end.2005.19.813.pd

Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C‐kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106819/1/j.1365-2559.2011.03753.x.pd

Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway

BACKGROUND: Genetic studies associated the CAPB locus with familial risk of brain and prostate cancers. We have identified HSPG2 (Perlecan) as a candidate gene for CAPB. Previously we have linked Perlecan to Hedgehog signaling in Drosophila. More recently, we have demonstrated the importance of Hedgehog signaling in humans for advanced prostate cancer. RESULTS: Here we demonstrate Perlecan expression in prostate cancer, and its function in prostate cancer cell growth through interaction and modulation of Sonic Hedgehog (SHH) signaling. Perlecan expression in prostate cancer tissues correlates with a high Gleason score and rapid cell proliferation. Perlecan is highly expressed in prostate cancer cell lines, including androgen insensitive cell lines and cell lines selected for metastatic properties. Inhibition of Perlecan expression in these cell lines decreases cell growth. Simultaneous blockade of Perlecan expression and androgen signaling in the androgen-sensitive cell line LNCaP was additive, indicating the independence of these two pathways. Perlecan expression correlates with SHH in tumor tissue microarrays and increased tumor cell proliferation based on Ki-67 immunohistochemistry. Inhibition of Perlecan expression by siRNA in prostate cancer cell lines decreases SHH signaling while expression of the downstream SHH effector GLI1 rescues the proliferation defect. Perlecan forms complexes with increasing amounts of SHH that correlate with increasing metastatic potential of the prostate cancer cell line. SHH signaling also increases in the more metastatic cell lines. Metastatic prostate cancer cell lines grown under serum-starved conditions (low androgen and growth factors) resulted in maintenance of Perlecan expression. Under low androgen, low growth factor conditions, Perlecan expression level correlates with the ability of the cells to maintain SHH signaling. CONCLUSION: We have demonstrated that Perlecan, a candidate gene for the CAPB locus, is a new component of the SHH pathway in prostate tumors and works independently of androgen signaling. In metastatic tumor cells increased SHH signaling correlates with the maintenance of Perlecan expression and more Perlecan-SHH complexes. Perlecan is a proteoglycan that regulates extracellular and stromal accessibility to growth factors such as SHH, thus allowing for the maintenance of SHH signaling under growth factor limiting conditions. This proteoglycan represents an important central regulator of SHH activity and presents an ideal drug target for blocking SHH effects

The quality of surgical pathology care for men undergoing radical prostatectomy in the U.S.

BACKGROUND. The authors assessed adherence with the College of American Pathologists (CAP) radical prostatectomy (RP) practice protocol in a national sample of men who underwent RP for early-stage prostate cancer. METHODS. Using the National Cancer Data Base, the authors identified a nationally representative sample of 1240 men (unweighted) who underwent RP. For each patient, local cancer registrars performed an explicit medical record review to assess patient-level compliance with surgical pathology report documentation of 7 morphologic criteria (ie, quality indicators). Applying the CAP prognostic factor classification framework, composite measures and all-or-none measures of quality indicator compliance were calculated for the following analytic categories: 1) a strict subset of CAP category I prognostic factors (3 indicators), 2) a broad subset of CAP category I factors (6 indicators), and 3) the full set of 7 indicators. RESULTS. Among a weighted sample of 24,420 patients who underwent RP, compliance with documentation of the CAP category I factors varied from 54% (95% confidence interval [95% CI], 50–58%) for pathologic tumor, lymph node, metastases classification (according to the American Joint Committee on Cancer staging system) to 97% (95% CI, 96–99%) for Gleason score. In composite, RP pathology reports contained 83% (95% CI, 81–84%), 85% (95% CI, 84–87%), and 79% (95% CI, 78–80%) of the recommended data elements measured by the strict CAP category I subset, the broad CAP category I subset, and the full set of 7 indicators, respectively. In contrast to the generally higher composite scores, only 52% (95% CI, 48–56%) and 41% (95% CI, 37–45%) of men who underwent RP had complete documentation in their pathology reports for the strict and broad CAP category I subsets, respectively. CONCLUSIONS. RP surgical pathology reports contained most of the recommended data elements; however, the frequent absence of pathologic stage provides an opportunity for quality improvement. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56046/1/22698_ftp.pd

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

Localized Amyloidosis of the Upper Urinary Tract: A Case Series of Three Patients Managed with Reconstructive Surgery or Surveillance

Abstract Objective: To evaluate the clinical presentation, diagnosis, treatment, and prognosis of primary localized amyloidosis of the upper urinary tract. Methods: Patients with primary localized amyloidosis of the upper urinary tract were identified by database inquiry, and their medical records were reviewed. Results: Primary localized amyloidosis was identified in the ureter in two patients and in the renal pelvis in one patient. Systemic disease and amyloidosis secondary to a medical condition were excluded. All three patients presented with gross painless hematuria, and two also reported flank pain. None endorsed irritative urinary symptoms. Initial evaluation consisted of renal ultrasonography or intravenous urogram, and subsequently additional imaging and ureteroscopies with biopsies were performed. Congo red staining of the biopsies displayed apple green birefringence under polarized light. One patient was treated with distal ureterectomy and Boari flap ureteroneocystostomy, whereas the other two were followed with surveillance imaging. None of the patients have developed progressive disease or recurrence of their symptoms during follow-up of 15 months, 6 years, and 8 years. Conclusions: Primary localized amyloidosis of the upper urinary tract is a rare condition that is of interest because the clinical presentation and radiographic and endoscopic appearance mimic malignancy. Many commonalities exist between upper urinary tract and bladder amyloidosis, but obstructive features, like flank pain and hydronephrosis, are unique to upper urinary tract lesions. In the absence of significant obstruction, early eradication of an upper urinary tract lesion may not be necessary. Rather, follow-up with serial imaging is sufficient to monitor for disease progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85121/1/end_2009_0383.pd

Chroma Analysis for Quantitative Immunohistochemistry using Active Learning

Protein expression analysis has traditionally relied upon visual evaluation of immunohistochemical reaction by a pathologist, who analyzes the grade of staining intensity and estimates the percentage of cells stained in the area of interest. This method is effective in experienced hands but has potential limitations in its reproducibility due to subjectivity between and within operators. These limitations are particularly pronounced in gray areas where a distinction of weak from moderate protein expression can be clinically significant. Some research also suggests that sub localization of the protein expression into different components such as nuclei versus cytoplasm may be of great importance. This distinction can be particularly difficult to quantify using manual methods. In this paper, we formulate the problem of quantitative protein expression analysis as an active learning classification problem, where a very small set of pre-sampled user data is used for understanding expert evaluation. The expert coveted confidence is mapped to derive an uncertainty region to select the supplemental learning data. This is done by posing a structured query to the unknown data set. The newly identified samples are then augmented to the training set for incremental learning. The strength of our algorithm is measured in its ability to learn with minimum user interaction. Chroma analysis results of a Tissue Micro-array (TMA) images are presented to demonstrate the user interaction and learning ability. The chroma analysis results are then processed to obtain quantitative results

Renal Metastasis from Hurthle Cell Thyroid Carcinoma and Its Evaluation with Hybrid Imaging

Background: In general, thyroid carcinomas, when they behave aggressively, metastasize to lungs and occasionally to bone and brain. Metastases to other organs are distinctly unusual. Renal metastases have been reported in only 10 patients. Here we report, to the best of our knowledge, the first patient with Hurthle cell thyroid cancer and renal metastasis. The evaluation of this patient was enhanced by utilizing a variety of imaging techniques. Summary: The patient was a 75-year-old man who had a history of a total thyroidectomy 9 years previously for a right thyroid lobe Hurthle cell carcinoma. He postoperatively received 150?mCi (5550?MBq) of 131-I therapy and was maintained on thyrotropin suppressive therapy with levothyroxine. He presented to us with a recent history of a progressively enlarging left neck mass. The serum thyroglobulin was elevated to 1183?ng/mL. Multimodality imaging with fluorodeoxyglucose positron emission tomography?computed tomography, magnetic resonance imaging, and Somatostatin receptor scintigraphy with single photon emission computed tomography (SPECT)-computed tomography revealed numerous foci in the skeleton and right kidney. Anatomic imaging characteristics favored a primary renal cell cancer with the additional evidence of renal vein invasion and thrombosis. Histology later revealed a metastatic renal Hurthle cell cancer with positive thyroglobulin stains. Several of the skeletal foci responded partially to cryoablative therapy. The patient refused noncurative Somatostatin analog therapy. He is alive and doing well clinically. Conclusion: The management of thyroid cancers in high-risk groups, such as our patient, frequently requires expert management by the use of novel multimodality imaging and therapeutic techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85140/1/thy_2009_0326.pd