Clinical Significance of Alterations of Chromosome 8 in High-Grade, Advanced, Nonmetastatic Prostate Carcinoma

Context.—Loop electrosurgical excision procedure (LEEP) is a therapeutic option following biopsy diagnosis of high-grade squamous intraepithelial lesion (HSIL). Most LEEPs will confirm the HSIL biopsy diagnosis but a number of them will not. Such negative findings suggest the possibility of an incorrect biopsy diagnosis, removal of the lesion by biopsy, or insufficient LEEP sampling. Objective.—To determine the frequency of negative LEEP findings following HSIL biopsies and better understand the clinical significance of negative LEEP findings. Design.—The Department of Pathology's records were searched for all patients undergoing LEEP excision who had prior cervical biopsies and subsequent clinical follow-up. Results.—Three hundred seventy-eight women were found who had index biopsies, subsequent LEEPs, and clinical follow-up averaging 25.8 months. Three hundred six women had HSIL on biopsy with 223 (73%) showing HSIL on LEEP. Seventy-three (24%) LEEPs in women with HSIL index biopsy results yielded negative findings or disclosed low-grade squamous intraepithelial lesion (LSIL). Twenty-nine of 223 patients (13%) with an HSIL result both on biopsies and LEEPs had HSIL on biopsy and/or excisional clinical follow-up. Seven of 73 patients (10%) with positive (HSIL) biopsy results but negative LEEP findings or LSIL had HSIL on biopsy and/or excisional follow-up. Conclusions.—Twenty-four percent of patients with HSIL on biopsy had negative findings or LSIL on LEEP. There is no statistical difference in development of HSIL after LEEP for those with positive biopsy and positive LEEP results (13%) versus positive biopsy and negative LEEP results (10%). The occurrence of a negative LEEP finding following a positive biopsy finding was frequent (24%) and does not portend a different clinical follow-up from a positive biopsy and positive LEEP result.

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Molecular Analysis of the t(2;8)/MYC-IGK Translocation in High-Grade Lymphoma/Leukemia by Long-Distance Inverse PCR

Blood ◽

10.1182/blood.v118.21.4407.4407 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4407-4407

Author(s):

Hannes Kroenlein ◽

Stefan Schwartz ◽

Richard Reinhardt ◽

Mara Molkentin ◽

Nicola Goekbuget ◽

...

Keyword(s):

Molecular Analysis ◽

Gene Locus ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Chromosome 8 ◽

Chromosomal Translocations ◽

High Grade ◽

Long Distance ◽

Chromosomal Breakpoints ◽

Pcr Method

Abstract Abstract 4407 Background: Burkitt lymphoma and a subset of diffuse large B-cell lymphomas are characterized by chromosomal alterations affecting the MYC oncogene on 8q24. In most cases MYC is found juxtaposed to the immunoglobulin heavy chain (IGH) gene locus. Translocations to the immunoglobulin kappa (IGK) gene locus on 2p11 are observed in around 10% of cases. Little data exist on the molecular mechanisms leading to this aberration. The chromosomal breakpoints on chromosome 8 have been found dispersed over a large area 3’ of MYC. Currently, molecular cytogenetics (FISH) and cytogenetics are the methods of choice to detect the t(2;8) translocation and until now there exists no PCR method to reliably detect it. Objectives: In order to obtain a better understanding of this chromosomal translocation we developed a long-distance inverse (LDI) PCR method for the identification of chromosomal translocations affecting the IGK locus. The LDI PCR method takes advantage of the fact that the chromosomal breaks occur on chromosome 2 in the vicinity of the IGK joining segments. Using this method we investigated a number of cytogenetically mostly uncharacterized high-grade lymphoma samples. Results: A MYC-IGK juxtaposition was identified in 7 patients and three t(2;8)-positive cell lines. The chromosomal breakpoints were molecularly characterized and analyzed. The linear distance of the breakpoints on chromosome 8 to MYC ranged from some 100 bp to more than 0.5 MB. The breakpoints appeared to be clustered in distinctive regions, however, the number is still to small to draw definitive conclusions. The reciprocal translocated allele could be characterized in the majority of cases and putative break mechanisms are proposed. No larger sequence homologies were detected at the break sites. A minority of breaks were located near putative recombination signal sequences (RSS). Conclusions: This study represents the largest series of t(2;8)-positive cases analyzed so far and the LDI PCR developed therein is the first universally applicable PCR-based method to detect this aberration. This LDI PCR should furthermore in general be useful for the molecular analysis of chromosomal translocations affecting the IGK locus. These aberrations have been detected in various lymphoma entities but are currently largely unexplored. Disclosures: No relevant conflicts of interest to declare.

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Clinical significance of the diagnosis of low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion

Cancer Cytopathology ◽

10.1002/cncy.20004 ◽

2009 ◽

Vol 117 (2) ◽

pp. 92-100 ◽

Cited By ~ 13

Author(s):

Mariam Alsharif ◽

Klint Kjeldahl ◽

Colleen Curran ◽

Shelby Miller ◽

H. Evin Gulbahce ◽

...

Keyword(s):

Clinical Significance ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Intraepithelial Lesion

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The Clinical Significance of a Negative Loop Electrosurgical Cone Biopsy for High-Grade Dysplasia

Obstetrics and Gynecology ◽

10.1097/01.aog.0000132803.88049.84 ◽

2004 ◽

Vol 104 (2) ◽

pp. 250-254 ◽

Cited By ~ 26

Author(s):

Chad A. Livasy ◽

Dominic T. Moore ◽

Linda Van Le

Keyword(s):

Clinical Significance ◽

High Grade Dysplasia ◽

High Grade ◽

Cone Biopsy

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The role of high-grade prostatic intraepithelial neoplasia for biochemical relapse of prostate carcinoma after radical prostatectomy

Medicina ◽

10.3390/medicina46090085 ◽

2010 ◽

Vol 46 (9) ◽

pp. 604 ◽

Cited By ~ 4

Author(s):

Stasys Auškalnis ◽

Daimantas Milonas ◽

Mindaugas Jievaltas ◽

Kęstutis Vaičiūnas ◽

Antanas Mickevičius ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Differentiation ◽

Radical Prostatectomy ◽

Gleason Score ◽

Prostate Carcinoma ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

Tnm Stage ◽

High Grade ◽

Biochemical Relapse

The objective of the study was to evaluate the relationship between high-grade intraepithelial neoplasia diagnosed after radical retropubic prostatectomy and the clinical and pathological characteristics of prostate cancer, and to evaluate the time to biochemical relapse of the disease within the groups of high-grade prostatic intraepithelial neoplasia (HGPIN) and non-HGPIN patients. Material and methods. Patients, clinically diagnosed with local prostate carcinoma at the Clinic of Urology, Kaunas University of Medicine, during 2003–2007 and treated with radical retropubic prostatectomies, were distributed into two groups according to the HGPIN detected in the postoperative material: HGPIN and non-HGPIN. The two groups were compared in terms of preoperative and postoperative characteristics. The patients who were followed up for at least 12 months were included into the study. The biochemical relapse of prostate cancer was determined if there were two consecutive rises of prostate-specific antigen (PSA) level above 0.2 ng/mL or according to the attending physician’s opinion, there was a need for adjuvant treatment even with onetime rise of PSA level above 0.2 ng/mL. Results. There was no significant difference between the HGPIN and non-HGPIN groups in terms of time to biochemical relapse and frequency of biochemical relapses, time before surgery, the timing of the HGPIN diagnosis, age, or PSA level. After radical prostatectomy, patients in the HGPIN group were found to have significantly more often poorer cancer cell differentiation according to the Gleason score (≥7 vs. <7; P=0.001) and higher TNM stage (T3a,b vs. T2a,b,c; P=0.001). Fewer positive resection margins were diagnosed in the HGPIN group (P=0.05). The groups did not differ in terms of the degree of differentiation according to the Gleason score or perineural invasion (P=0.811 and P=0.282, respectively). Conclusions. HGPIN was more often associated with the characteristics of the poor prognosis for relapse of prostate cancer: poorer tumor cell differentiation according to the Gleason score and more cases of higher TNM stage. HGPIN did not have any influence on biochemical relapse of the disease during the short-term follow-up.

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Chromosome 8 Polysomy Accounting for MYC Over-Expression in Angiosarcoma Arising as Somatic-Type Malignancy in Metastatic Teratoma. Case Report

International Journal of Surgical Pathology ◽

10.1177/10668969211067762 ◽

2021 ◽

pp. 106689692110677

Author(s):

A. Cristina Vargas ◽

Peter Grimison ◽

Christopher Joy ◽

Bernadette Garrone ◽

Fiona Bonar ◽

...

Keyword(s):

Case Report ◽

Surrogate Marker ◽

Chromosome 8 ◽

High Grade ◽

Clinical Scenario ◽

Germ Cell Tumours ◽

Over Expression ◽

Post Irradiation ◽

Chronic Lymphedema

MYC over-expression by immunohistochemistry (IHC) is utilised in routine pathology practice as a surrogate marker for MYC amplification, which plays a key oncogenic role in post-irradiation and chronic lymphedema-associated angiosarcoma. We present the case of a 32-year old male, who presented with high-grade angiosarcoma arising in a background of metastatic testicular teratoma. IHC for MYC showed strong nuclear expression in the angiosarcoma cells prompting the consideration of post-irradiation-induced angiosarcoma but our patient did not undergo radiotherapy. Fluorescence in-situ hybridization (FISH) excluded MYC amplification and instead showed Chromosome 8 polysomy, which accounted for the strong MYC IHC expression present, not previously described in the context of germ cell tumours. The occurrence of MYC over-expression due to polysomy illustrates a novel clinical scenario (angiosarcoma arising as somatic malignancy) where strong MYC IHC expression can be found in the absence of underlying amplification or prior radiotherapy exposure.

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