Prognostic Markers in Peripheral T-Cell Lymphoma

Based on their own experience and knowledge of the literature, the authors review the pathobiological characteristics of peripheral T-cell lymphomas (PTCLs), focusing on the available prognostic indicators. The International Prognostic Index (IPI), which is based on age, performance status, lactate dehydrogenase [LDH], stage, and extranodal involvement, appears to be efficient as a prognostic index for PTCLs, at least in part and especially for certain PTCL subtypes. However, it is not so satisfactory for the two commonest PTCLs, PTCL not otherwise specified (PTCL/NOS) and angioimmunoblastic T-cell lymphoma (AITL), for which novel scores, possibly based on the biologic features of the tumors, have been explored. An Italian cooperative group proposed a revision of the IPI for PTCL unspecified (PTCL-U), the Prognostic Index for PTCL-U (PIT), which includes age, performance status, LDH, and bone marrow involvement. The PIT apparently offered some advantages, but they were not confirmed in subsequent studies. A clinical-biological score (the Bologna score) was then proposed, including tumor proliferation and clinical features (age, LDH, and performance status). This score appears promising and offers the intriguing advantage of integrating biological and clinical elements, but independent validation on a large series is still warranted. More recently, gene expression profiling has been used to identify novel molecular prognostic factors. In particular, inactivation of the NFκB pathway, high expression of proliferation-associated genes, and cytotoxic molecular phenotype seem to be associated with a worse outcome. So far, however, none of these indicators has been validated in an independent series. Finally, various reports have dealt specifically with the prognostication of NK-derived tumors, including nasal and nasal-type lymphomas. Both the IPI and dedicated models have turned out to be of prognostic relevance for these tumors. In conclusion, although the IPI is somewhat effective for PTCL prognostication, novel scores that are more refined and possibly disease-specific are warranted. The validation process for several models, including clinical-pathological and molecular models, is now ongoing.     

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

To better define the significance of proliferation centers (PCs), the morphological hallmark of chronic lymphocytic leukemia (CLL), lymph node biopsies taken from 183 patients were submitted to histopathologic and fluorescence in situ hybridization (FISH) studies using a 5-probe panel on tissue microarrays. Seventy-five cases (40.9%) with confluent PCs were classified as 'PCs-rich' and 108 cases (59.1%) with scattered PCs were classified as 'typical'. Complete FISH data were obtained in 101 cases (55.1%), 79 of which (78.2%) displayed at least one chromosomal aberration. The incidence of each aberration was: 13q- 36,7%, 14q32 translocations 30.8%, 11q- 24.7%, trisomy 12 19.5% and 17p- 15.6%. Five cases showed extra copies of the 14q32 region. The 'PCs-rich' group was associated with 17p-, 14q32/IgH translocation, +12, Ki-67>30%. The median survival from the time of tissue biopsy for PCs-rich and typical groups was 11 and 64 months, respectively (P=0.00001). The PCs-rich pattern was the only predictive factor of an inferior survival at multivariate analysis (P=0.022). These findings establish an association between cytogenetic profile and the amount of PC in CLL, and show that this histopathologic characteristic is of value for risk assessment in patients with clinically significant adenopathy.     

Evaluation of Modified PEG-Anilinoquinazoline Derivatives as Potential Agents for EGFR Imaging in Cancer by Small Animal PET

Purpose

The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with ¹²⁴I, ¹⁸F, and ¹¹C as potential positron emission tomography (PET) bioprobes for visualizing epidermal growth factor receptor (EGFR) in cancer using small animal PET.

Procedures

Xenograft mice with the human glioblastoma cell lines U138MG (lacking EGFR expression) and U87MG.wtEGFR (transfected with an overexpressing human wild-type EGFR gene) were used. Static and dynamic PET imaging was conducted for all three PEGylated compounds. Tumor necrosis, microvessel density, and EGFR levels were evaluated by histopathology and enzyme-linked immunosorbent assay.

Results

Nineteen animal models were generated (two U138MG, three U87MG, 14 with both U138MG and U87MG bilateral masses). In static images, a slight increase in tracer uptake was observed in tumors, but in general, there was no retention of tracer uptake over time and no difference in uptake between U138MG and U87MG masses. In addition, no significant uptake was demonstrated in dynamic scans of the ¹⁸F-PEG tracer. No necrosis was present except in four animals. MVD was 9.6 and 48 microvessels/×400 field in the U138GM and U87GM masses, respectively (p?=?0.00008). Similarly, the microvessel grades were generally higher in the U87GM group (p?=?0.002). Total EGFR amount was higher in U87MG than U138MG masses (p?=?0.001), but the ratio of activated (pY1068) to total EGFR did not differ (p?=?0.95).

Conclusions

PEGylated tracers labeled with ¹¹C, ¹²⁴I, and ¹⁸F showed no significant difference in uptake between U138MG and U87MG glioblastoma xenograft mice. The tracer binding with EGFR could be influenced by activation of the tyrosine kinase portion of the receptor which was similar in U138MG and U87MG. Despite these results, these tracers should be investigated in animal models with mutant EGFR genes to determine whether aberrant receptor function plays a role in tumor uptake.     

Pigmented villonodular synovitis of the hip: 2- to 23-year followup study.

Pigmented villonodular synovitis affecting the hip is rare. Seven new patients are presented and 117 cases from the literature are reviewed. Among the new patients, two refused treatment; in one patient, severe bone loss was observed after a radiographic followup of 21 years; the second patient showed no radiographic changes 2 years after diagnosis. One patient underwent a synovectomy and had a recurrence 9 years later, requiring a total hip replacement. The remaining four patients underwent synovectomy and primary total hip replacement with no recurrences detected after an average followup of 13 years (range, 2-23 years). Among 117 cases published, 62 patients (53%) did not have enough information for analysis. A metaanalysis using the remaining 55 patients was done. In nine patients (16%; nine of 55) the diagnosis was made with a preoperative biopsy. Treatment consisted of synovectomy in 26 patients (47%; 26 of 55), arthroplasty in 24 (43%; 24 of 55), arthrodesis in two (4%; two of 55), and hindquarter amputation in a patient misdiagnosed as having synovial sarcoma (2%; one of 55). Two patients (4%; two of 55) were not treated. Ten patients had a recurrence (19%; 10 of 53); nine in the synovectomy group (35 %; nine of 26) and one in the joint replacement group (4%; one of 24). Synovectomy is recommended for patients with preserved articular cartilage and total hip replacement is recommended for patients with secondary osteoarthritis. Removal of all macroscopic tumors including careful curetting of the osteolytic lesions should be done as they may constitute a source of recurrence.     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.