Dose to the dominant intraprostatic lesion using HDR vs. LDR monotherapy: A Phase II randomized trial.

PURPOSE: To present the dosimetric results of a Phase II randomized trial comparing dose escalation to the MRI-defined dominant intraprostatic lesion (DIL) using either low-dose-rate (LDR) or high-dose-rate (HDR) prostate brachytherapy. MATERIAL AND METHODS: Patients receiving prostate brachytherapy as monotherapy were randomized to LDR or HDR brachytherapy. Prostate and DILs were contoured on preoperative multiparametric MRI. These images were registered with transrectal ultrasound for treatment planning. LDR brachytherapy was preplanned using I-125 seeds. HDR brachytherapy used intraoperative transrectal ultrasound-based planning to deliver 27 Gy/2 fractions in separate implants. DIL location was classified as peripheral, central, or anterior. A student t-test compared DIL D90 between modalities and DIL locations. RESULTS: Of 60 patients, 31 underwent LDR and 29 HDR brachytherapy. Up to three DILs were identified per patient (100 total) with 74 peripheral, six central, and 20 anterior DILs. Mean DIL volume was 1.9 cc (SD: 1.7 cc) for LDR and 1.6 cc (SD 1.3 cc) for HDR (p = 0.279). Mean DIL D90 was 151% (SD 30%) for LDR and 132% (SD 13%) for HDR. For LDR, mean peripheral DIL D90 was 159% (SD 27%) and central or anterior 127% (SD 13%). HDR peripheral DILs received 137% (SD 12%) and central or anterior 119% (SD 7%). DIL D90 for peripheral lesions was higher than anterior and central (p < 0.001). CONCLUSIONS: DIL location affects dose escalation, particularly because of urethral proximity, such as for anterior and central DILs. HDR brachytherapy may dose escalate better when target DIL is close to critical organs.

Mucinous tubular and spindle cell carcinoma of kidney without sarcomatoid change showing metastases to liver and retroperitoneal lymph node.

Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon, newly recognized tumor that in its classic histological form shows tightly packed, elongated tubules with transition into spindle cell areas and pale mucinous stroma. The current data suggest that the great majority of MTSCCs have a favorable prognosis; however, the follow-up data are limited and the full biologic potential of this tumor remains to be established. There are a few examples of MTSCCs metastatic to lymph nodes and rare cases with sarcomatoid differentiation associated with distant metastases. We report on a case of MTSCC of kidney with concurrent nodal and liver metastases. The metastatic nodules were well circumscribed and showed morphological and immunophenotypic features similar to those of the primary tumor. Extensive sampling revealed no evidence of sarcomatoid morphology. To our knowledge, this is the first case of MTSCC without sarcomatoid differentiation showing parenchymal metastasis.

Encapsulated apocrine papillary carcinoma of the breast--a tumour of uncertain malignant potential: report of five cases.

Five cases of an unusual encapsulated apocrine papillary tumour are reported. All presented as cystic masses in the breast of women aged 44-84 years. Imaging studies showed a complex cyst often with one or more mural nodules. The key histological features are similar to those of classical encapsulated papillary carcinoma in that myoepithelial cells were absent within the papillary structures and at the periphery of the cyst. All were pure apocrine in type and showed variable degrees of cytological atypia and mitotic activity. All lacked evidence of malignancy in the breast tissue outside of the lesion. Sentinel lymph node biopsies performed in three of the cases were negative for metastases, and all have behaved in a benign fashion.

Minimum altered regions in early prostate cancer progression identified by high resolution whole genome tiling path BAC array comparative hybridization.

BACKGROUND: Carcinoma of the prostate (CaP) is a serious health problem. The altered molecular mechanisms that lead to this disease are poorly understood. METHODS: Specimens from radical prostatectomies and blood were collected from 18 CaP surgery patients. For CGH studies, 20 CaP-related samples (16 Gleason grade 3, 3 higher grades, 1 BPH sample) and 18 samples of patient-matched normal epithelial cells were obtained by laser-assisted microdissection from frozen sections of the 18 prostatectomy specimens. High resolution SMRT aCGH was used to compare genomic profiles of prostatic samples to patient-matched blood and pooled female DNA. TMPRSS2-ERG fusion transcript analysis was performed by RT-PCR in relation to alterations detected at the TMPRSS2 locus. RESULTS: Our comprehensive aCGH approach allowed us to define 35 regions of recurrent alterations while excluding germline copy number polymorphisms. Novel regions identified include 2q14.2, containing INHBB, and 17q21.31. The TMPRSS2 locus at 21q22.3 may be a hotspot for rearrangements with 75% of the alterations resulting in the expression of a TMPRSS2-ERG fusion transcript. Differences in fusion expression in different areas in an individual tumor focus and expression in adjacent normal epithelium supported intrafocal heterogeneity and field cancerization, respectively. Both features challenge our efforts to develop more objective markers for diagnosis and prediction of the severity of CaP. CONCLUSION: The high-density array enabled precise mapping of genomic alterations and consequently definition of minimum altered regions smaller than previously reported thus facilitating identification of those genes that contribute to the cancer transformation process.

DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer.

Identification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high-grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR-based technique called scanning of microdissected archival lesion (SMAL)-PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y-box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL-PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis.

Clinical impact of second pathology opinion: a longitudinal study of central genitourinary pathology review before prostate brachytherapy.

PURPOSE: To evaluate the clinical impact of pathology review before prostate brachytherapy. METHODS AND MATERIALS: Original and reviewing pathologists' reports were retrospectively collected from 1323 men treated with prostate brachytherapy between July 1998 and October 2005 at one institution. Statistical analysis was performed pre- and post-January 2002. The clinical impact of pathology review was evaluated. RESULTS: Gleason Score (GS) change (GS(Delta)) occurred in 25.2% (334) of cases; GS increased in 21.6%, decreased in 2.4%, and diagnosed malignancy in 1.2% of cases. Post-2002, concordance in attributed GS improved, with GS(Delta) of 31.9-20.6%, respectively (p<0.001), and a reduction in the average GS(Delta) (p<0.001). The clinical impact was substantial with management changing in 14.8% of cases. CONCLUSION: Concordance between the original and reviewing pathologists' GS has improved during the study period. Nevertheless, discordance persists in one of five cases. Pathology review remains essential, if treatment decisions hinge on GS.

Protein profiling of microdissected prostate tissue links growth differentiation factor 15 to prostate carcinogenesis.

Identification of proteomic alterations associated with early stages in the development of prostate cancer may facilitate understanding of progression of this highly variable disease. Matched normal, high-grade prostatic intraepithelial neoplasia (hPIN) and prostate cancer cells of predominantly Gleason grade 3 were procured by laser capture microdissection from serial sections obtained from snap-frozen samples dissected from 22 radical prostatectomy specimens. From these cells, protein profiles were generated by surface-enhanced laser desorption/ionization-time of flight mass spectrometry. A 24-kDa peak was observed at low or high intensity in profiles of prostate cancer cells in 19 of 27 lesions and at low intensity in 3 of 8 hPIN lesions but was not detectable in matched normal cells. SDS-PAGE analysis of prostate cancer and matched normal epithelium confirmed expression of a prostate cancer-specific 24-kDa protein. Mass spectrometry and protein data-based analysis identified the protein as the dimeric form of mature growth differentiation factor 15 (GDF15). The increased expression of mature GDF15 protein in prostate cancer cells cannot be explained on the basis of up-regulation of GDF15 mRNA because reverse transcription-PCR analysis showed similar amounts of transcript in normal, hPIN, and prostate cancer cells that were obtained by laser capture microdissection in the same set of serial sections from which the protein profiles were obtained. Our findings suggest that early prostate carcinogenesis is associated with expression of mature GDF15 protein.