Biomedical subjects

Louis Guillou

Publications and source records attributed to Louis Guillou.

At least 37 records · Page 2Linked to original sources

PubMed2004

ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications.

Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors.

Abdominal Neoplasms↗

PubMed2004

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity.

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.

Adult↗

PubMed2004

Digestive PEComas: a solution when the diagnosis fails to "fit".

We report two cases of digestive/intra-abdominal PEComa. The first lesion developed in the caecum of a 36-year-old woman, the second in the pararectal region of a 35-year-old woman. The first tumor was formed from spindle cells arranged in fascicles, the second contained predominantly epithelioid cells with prominent nucleoli. Immunohistochemically, tumor cells expressed smooth muscle actin and melanocyte markers (HMB45), S-100 protein and CD117 were negative. Based on the morphologic aspect and, above all, on the immunohistochemical study the diagnosis of PEComa was retained for both lesions. In the gastrointestinal tract, the principal differential diagnoses of PEComas are gastrointestinal stromal tumors, particularly the round cell/epithelioid subtype, and metastases of carcinoma and melanoma. Other differential diagnoses include rhabdomyosarcoma, paraganglioma, leiomyosarcoma, and clear cell sarcoma.

Abdominal Neoplasms↗

PubMed2004

Human herpesvirus 8 immunostaining: a sensitive and specific method for diagnosing Kaposi sarcoma in paraffin-embedded sections.

Human herpesvirus 8 (HHV-8) is recognized as a major causal agent of Kaposi sarcoma (KS), and it has been detected in all epidemiologic variants of KS. Until now, detection of HHV-8 in paraffin-embedded sections was done mostly by using reverse transcriptase-polymerase chain reaction. To assess the sensitivity and specificity of an anti-HHV-8 antibody and its potential usefulness for separating KS from its mimickers, we immunostained 72 KS samples and 108 samples of potential mimickers of KS with the monoclonal antibody latent nuclear antigen-1 (LNA-1; Advanced Biotechnologies, Columbia, MD). Cases of KS included all epidemiologic variants of the disease. Non-KS lesions included 34 angiosarcomas, 4 kaposiform hemangioendotheliomas, and 70 various benign vascular lesions. Immunostaining for CD31, CD34, and/or von Willebrand factor (factor VIII) also were performed in all cases. All but 1 case of KS (sensitivity, 99%) and none of the non-KS lesions (specificity, 100%) stained with the LNA-1 anti-HHV-8 antibody. The LNA-1 anti-HHV-8 antibody is a reliable marker of all variants of KS. Because KS mimickers are consistently negative for this marker, its use for diagnostic purposes is recommended.

Adult↗

PubMed2003

The TPTE gene family: cellular expression, subcellular localization and alternative splicing.

The human TPTE (Transmembrane Phosphatase with TEnsin homology) gene family encodes a PTEN-related tyrosine phosphatase with four potential transmembrane domains. Chromosomal mapping revealed multiple copies of the TPTE gene on chromosomes 13, 15, 21, 22 and Y. Human chromosomes 13 and 21 copies encode two functional proteins, TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) and TPTE, respectively, whereas only one copy of the gene exists in the mouse genome. In the present study, we show that TPTE and TPIP proteins are expressed in secondary spermatocytes and/or prespermatids. In addition, we report the existence of several novel alternatively spliced isoforms of these two proteins with variable number of transmembrane domains. The latter has no influence on the subcellular localization of these different peptides as shown by co-immunofluorescence experiments. Finally, we identify another expressed TPTE copy, mapping to human chromosome 22, whose transcription appears to be under the control of the LTR of human endogenous retrovirus RTVL-H3.

Alternative Splicing↗

PubMed2003

Should molecular testing be required for diagnosing synovial sarcoma? A prospective study of 204 cases.

BACKGROUND: The t(X;18) translocation is a specific marker of synovial sarcomas (SS). Detection of SYT-SSX transcripts by polymerase chain reaction (PCR) was tested on preselected specimens of well-established histologic types, but to our knowledge, the diagnostic utility of molecular assays on a series of potential SS in comparison with conventional tools has never been reported. METHODS: Two hundred four consecutive cases of potential SS submitted for a second opinion were studied prospectively. On the basis of clinical context, histologic aspect, and immunohistochemical profile, the tumors were divided into three categories: 1) diagnosis of SS certain, when the only possible diagnosis was SS; 2) diagnosis of SS probable, when SS was the first diagnosis contemplated, but a differential diagnostic issue was raised by other tumors; 3) diagnosis of SS possible, when the diagnosis of SS was not the first diagnosis considered. Detection of SYT-SSX transcripts was performed using real-time PCR from fixed, embedded tissue as a systematic test. RESULTS: Sufficient RNA samples were recovered for PCR from 177 specimens (87%). One hundred four specimens (51%) were positive for SYT-SSX transcripts. Tumor sites of SS included the extremities (n = 57), lung (n = 13), trunk wall (n = 12), head and neck (n = 6), and other sites (n = 16). There were 61 monophasic, 22 poorly differentiated, 17 biphasic, and 4 predominantly epithelial SS. For 58 tumor specimens (29%), diagnosis of SS was certain before molecular testing; 49 (84.5%) of these 58 contained SYT-SSX transcripts. For 39 tumor specimens (19%), diagnosis of SS was probable; 29 (74.4%) of these 39 contained SYT-SSX transcripts. For 107 tumor specimens (52%), diagnosis of SS was only possible and strongly challenged by another histologic type. The issue consisted mainly of making the distinction between an SS and a poorly differentiated spindle cell sarcoma (n = 49), a poorly differentiated round cell sarcoma (n = 34), a carcinoma (n = 11), a myoepithelioma (n = 8), or an epithelioid fibrosarcoma (n = 5).Twenty-six tumor specimens (24.3%) contained SYT-SSX transcripts-10, 7, 5, 3, and 1 in the spindle cell tumor, round cell tumor, carcinomalike tumor, myoepitheliomalike tumor, and epithelioid-fibrosarcoma-like tumor categories, respectively. CONCLUSIONS: Molecular testing was not required if the diagnosis of SS was certain or probable on the basis of clinical, histologic, and immunohistochemical evaluation. However, it proved to be very helpful or necessary when the diagnosis of SS was only possible and was challenged by other tumor types, mainly other spindle cell sarcomas, round cell sarcomas, carcinomas, myoepitheliomas, and epithelioid fibrosarcomas.

Adolescent↗

PubMed2003

Motility-related protein 1 (MRP-1/CD9) expression in urothelial bladder carcinoma and its relation to tumor recurrence and progression.

BACKGROUND: CD9 has been implicated in cell adhesion, motility, and proliferation, and numerous studies have demonstrated its prognostic value in different solid tumors. The objective of this study was to determine the relation of CD9 expression to tumor grade and tumor stage of urothelial carcinoma of the bladder and to define the value of CD9 in predicting the behavior of superficial papillary tumors (SPTs) (pathologic Ta [pTa] and pT1). METHODS: Three hundred twenty patients (118 patients with pTa tumors, 111 patients with pT1 tumors, and 91 patients with pT2 tumors) were examined for CD9 expression using immunohistochemistry applied on formalin fixed, paraffin embedded tissue. Patients were stratified into 3 categories, depending on CD9 expression: positive (> 50% positive cells), reduced (5-50% positive cells), or negative (< 5% positive cells). RESULTS: Loss of CD9 expression was found to be associated significantly with high-grade and high-stage urothelial tumors (P < 0.0001). A reduced/negative (altered) CD9 expression was associated with SPT progression, but not with recurrence (P < 0.001). Patients who had pTa or pT1 tumors with altered CD9 expression had a relative risk of 5.59 (P = 0.005; 95% confidence interval [95% CI], 1.69-18.48) for progression compared with patients who had tumors with positive CD9 expression. Kaplan-Meier curves showed that a lack of CD9 expression was associated significantly with progression free survival (P < 0.001; log-rank test), but not with recurrence. In patients with SPTs, multivariate Cox proportional hazards regression analysis revealed that negative CD9 expression was an independent prognostic marker for the prediction of tumor progression (P = 0.007; 95% CI, 0.11-0.70). CONCLUSIONS: In patients with urothelial bladder carcinoma, CD9 expression was associated significantly with tumor stage and grade, and a loss of CD9 expression was an independent prognostic factor for predicting progression in patients with SPTs. Thus, CD9 immunoexpression is a potential new predictor of tumor behavior in patients with SPTs of the urinary bladder.

Adult↗

PubMed2003

Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data--a study from the French Federation of Cancer Centers Sarcoma Group.

The clinicopathologic and immunohistochemical features of 28 dermatofibrosarcoma protuberans (DFSP), giant cell fibroblastomas (GCFs), and hybrid lesions occurring in children are presented, including molecular data for seven of them. There were 19 pure adult-type DFSP (9 male and 10 female patients aged between a few days [neonate] and 13 years, median 7 years), 5 pure GCF (all males aged from 2 to 8 years, median 4 years), and 4 hybrid tumors (all males aged from 1 to 4 years, median 2.5 years). Tumor locations in pure adult-type DFSP included the trunk (6) and lower (11) and upper (2) limbs. Pure GCFs were observed on the trunk (4) and knee (1), and hybrid lesions on the trunk (2) and lower (1) and upper (1) extremities. Tumor size (n = 20) ranged from 0.6 to 5 cm (median 2 cm). Histologically, pure DFSP presented as monotonous and infiltrative, low-grade, dermal/hypodermal storiform spindle cell proliferations, sparing adnexal structures. GCF showed a dense fibrous to myxoid matrix containing slender wavy spindle cells and multinucleated giant stromal cells often lining angiectoid spaces. Hybrid lesions showed varying combinations of DFSP and GCF areas. Mitotic activity ranged from 1 to 3 mitoses per 10 high power fields. All tumors were diffusely positive for vimentin and CD34 but negative for smooth muscle actin, desmin, epithelial membrane antigen, and cytokeratins; one pure adult-type DFSP was also S-100 protein positive; <1% of nuclei were Ki67 (Mib-1) positive. One karyotyped adult-type DFSP showed an unbalanced t(17;22) (q22;q13) translocation. Multiplex RT-PCR analysis and sequencing of PCR products in seven cases showed gene fusion transcripts in two pure DFSP, two pure GCFs, and one hybrid lesion. Results were uncertain in one pure GCF; one adult-type DFSP was negative. Treatment procedures were known for 27 patients, consisting of 16 wide excisions and 11 marginal excisions. Follow-up information on 15 widely excised tumors (median 24 months; range 5-144 months) showed no recurrence. Five of six marginally excised lesions with available follow up recurred 2 months to 6 years (median 2 years) after initial surgery; all but one were cured by wide reexcision. None of the tumors metastasized. In conclusion, this study emphasizes 1) the occurrence of adult-type DFSP in children, 2) the close relationship between DFSP and GCF clinically, histologically, and molecularly, 3) the excellent prognostic of these lesions if widely excised, and 4) the diagnostic usefulness of RT-PCR analyses in detecting the gene fusion transcripts resulting from the t(17;22) (q22;q13) in paraffin-embedded tissues.

Adolescent↗

PubMed2003

Short- and long-term prognostic value of postoperative cardiac troponin I concentration in patients undergoing coronary artery bypass grafting.

BACKGROUND: The value of postoperative cardiac troponin I (cTnI) has been shown to indicate a higher risk of in-hospital death after cardiac surgery. The authors therefore assessed the long-term prognostic value of cTnI in patients undergoing elective coronary artery bypass grafting. METHODS: Consecutive patients (n = 202) were included and divided into two groups according to the postoperative value of cTnI (< or >/= 13 ng/ml). In-hospital mortality and nonfatal cardiac events (delayed extubation > 24 h; postoperative requirement of inotropic agent; ventricular and supraventricular arrhythmia; postoperative myocardial infarction) were recorded. Survivors were then followed up over a 2-yr period. Data are median and odds ratio (95% confidence interval). RESULTS: Of all patients, 174 (86%) had a low cTnI (4.1 ng/ml; range, 1.1-12.6) and 28 (14%) had a high cTnI (23.8 ng/ml; range, 13.4-174.6). In-hospital mortality was not significantly different (4 vs. 2%), whereas long-term mortality (18 vs. 3%, P = 0.006) and mortality from cardiac cause (18 vs. 1%, P < 0.001) was greater in patients with a high cTnI. A high cTnI was a significant factor predicting death (odds ratio, 7.3 [2.0-27.1]) or death from cardiac causes (odds ratio, 37.4 [4.2-334.4]). Nonfatal cardiac events were also more frequent in the hospital (64 vs. 41%, P = 0.02) and within the 2-yr follow-up period (39% vs. 16%, P = 0.03) in patients with high cTnI. CONCLUSION: A high postoperative peak of cTnI is associated with increased risk of death, death from cardiac causes, and nonfatal cardiac events within 2 yr after coronary artery bypass grafting.

Aged↗

PubMed2003

Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study.

PURPOSE: We examined the sensitivity and specificity of Hexvix (PhotoCure ASA, Oslo, Norway) hexyl aminolevulinate (HAL) fluorescence cystoscopy in patients with superficial bladder cancer. MATERIALS AND METHODS: A total of 52 patients (38 men and 14 women) with a mean age of 72 years were investigated. HAL hydrochloride (100 mg dissolved in 50 ml phosphate buffer solution) (8 mM) was instilled into the bladder 1 hour prior to the endoscopic procedure. Cystoscopy was performed with the Storz D-light (Karl Storz, Tuttlingen, Germany) system, allowing inspection of the bladder wall under white and blue light (380 to 450 nm). RESULTS: A total of 422 biopsies obtained in fluorescing (165) and nonfluorescing (257) areas, including 5 random biopsies per patient, were analyzed to provide the best reference for the calculation of sensitivity and specificity. There were a total of 143 histologically verified tumors in 45 patients, including carcinoma in situ (CIS), Ta or T1 lesions. A total of 43 patients were diagnosed by fluorescence cystoscopy compared with 33 diagnosed by white light for 96% and 73% per-patient sensitivity, respectively. HAL cystoscopy was found particularly useful for finding CIS tumors. Of 13 patients with CIS tumors all except 1 were diagnosed or confirmed by HAL cystoscopy. HAL cystoscopy was well tolerated with no definite drug related adverse events reported, including effects on standard blood parameters. CONCLUSIONS: HAL fluorescence cystoscopy is a new, sensitive, promising diagnostic procedure that showed improved detection of bladder tumors, in particular CIS. The procedure is well tolerated and can easily be implemented in current clinical practice.

Aged↗

PubMed2003

[Recent entities in soft tissue tumor pathology. Part 2].

The second part of this review on the pathology of soft tissue tumors focuses on malignant entities of recent description, including the following: soft tissue giant cell tumor, inflammatory myxohyaline tumor, inflammatory fibroblastic sarcoma, low grade fibromyxoid Evans sarcoma and its variant, the hyalinizing spindle cell tumor with giant rosettes, spindle cell liposarcoma, proximal type epithelioid sarcoma, sclerosing epithelioid fibrosarcoma. For each entity, the diagnostic criteria, the clinical presentation and the differential diagnosis are described. The role of immunohistochemistry and molecular pathology in the identification and delineation of these new entities is emphasized.

Diagnosis, Differential↗

PubMed2002

Telomerase activity and hTERT mRNA expression can be heterogeneous and does not correlate with telomere length in soft tissue sarcomas.

In a previous study, we showed that telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA expression were undetectable in benign mesenchymal lesions and low-grade soft tissue sarcomas (STSs), but detectable in about 50% of intermediate-/high-grade STSs. We wondered if this lack of TA or hTERT mRNA expression could be related to the tumor sample examined and if there was a relationship between the former 2 parameters and telomere length. Two separate tumor samples from 37 STSs were examined for telomerase activity, using the telomerase repeat amplification protocol (TRAP) assay and for hTERT mRNA expression, using RT-PCR. Telomere length was determined in each tumor sample, using the terminal restriction fragments (TRF) technique. Significant variations in telomere length, TA and hTERT mRNA expression between 2 samples of the same tumor were observed in 27%, 11% and 27% of STSs, respectively. Telomere length did not correlate with TA or hTERT mRNA expression. Despite great intratumoral heterogeneity in telomere length, short and long telomeres were more often seen in the low/intermediate-grade and high-grade STS categories, respectively. Few STSs that showed a TRF pattern suggestive of alternative lengthening of telomeres (ALT) may contain ALT subpopulations.

Adolescent↗

PubMed2002

A subgroup of malignant fibrous histiocytomas is associated with genetic changes similar to those of well-differentiated liposarcomas.

Increasing clinical and pathological evidence suggests that malignant fibrous histiocytomas (MFH) comprise a heterogeneous tumor group. In a series of 108 MFH tested by comparative genomic hybridization, we found in 22 tumors high-level coamplification of the 12q14 approximately q15 chromosome region with other loci, a genetics strongly reminiscent of what has been observed for well-differentiated liposarcomas. Nevertheless, these MFH differ from liposarcomas by a high recurrence of coamplified partners because coamplified loci were seen at 1p32 in nine cases, 6q23 in seven cases, and 12q24 in six cases. The same recurrence was observed in a series of dedifferentiated liposarcomas, but not in a series of well-differentiated liposarcomas. These observations demonstrate that a subgroup of MFH share a genetic partner very similar to that observed in liposarcomas, and suggest that the undifferentiated status of these tumors is closely related to the amplifications of specific chromosome loci.

Allelic Imbalance↗

PubMed2002

Elevated (> or = 10%) MIB-1 proliferative index correlates with poor outcome in gastric stromal tumor patients: a study of 35 cases.

Mitotic activity and tumor size are currently regarded as the most powerful prognostic indicators for patients with gastrointestinal stromal tumor (GIST). This retrospective study evaluated the prognostic accuracy of MIB-1 proliferative index (PI) in combination with these two indicators in 35 GIST patients. Within a high-risk group, determined initially by tumor size and mitotic count, overall survival was significantly shorter for patients whose tumors had PI > or = 10% MIB-1 positive cells. When tumor location (gastric versus small intestine) was taken into account, a combination of tumor size, mitotic count, and PI > or = 10% identified a subgroup of patients with significantly shorter survival for gastric (but not small intestinal) GIST. Based on our results, MIB-1 immunostaining, when used in combination with tumor size and mitotic count, appears to be a powerful tool for identifying patients, especially those with gastric tumors, at high risk of recurrence and early tumor-related death.

Adult↗

PubMed2002

Malignant peripheral nerve sheath tumors are t(X;18)-negative sarcomas. Molecular analysis of 25 cases occurring in neurofibromatosis type 1 patients, using two different RT-PCR-based methods of detection.

To verify the absence of the synovial sarcoma translocation t(X;18) (SYT-SSX) in malignant peripheral nerve sheath tumors, 34 tumor samples from 25 neurofibromatosis type 1 patients were examined in two independent laboratories (Bordeaux, France, and Lausanne, Switzerland) using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques. RNA was extracted from paraffin blocks using standard methods, reverse transcribed, and conventional (in one laboratory) versus real-time (in the other laboratory) PCR performed. Twenty-seven tumor samples from 19 patients were negative for the t(X;18) in both laboratories; six additional tumors that were t(X;18)-negative in one laboratory gave noninterpretable results in the other, due to lack of internal positive controls; one case was noninterpretable in both places. In conclusion, malignant peripheral nerve sheath tumors in neurofibromatosis type 1 patients do not bear the synovial sarcoma t(X;18) (SYT-SSX). Laboratories that use PCR-based techniques for diagnostic purposes would benefit from quality assurance programs.

Adolescent↗

PubMed2002

Atheroembolization: a harmful complication of therapeutic internal iliac artery occlusion.

Coil embolization of the internal iliac artery (IIA) for proper endovascular treatment of aortoiliac aneurysms is a procedure with an acceptable morbidity rate consisting of buttock claudication in 12% to 55% and erectile dysfunction in 1% to 13%. Atheroembolic complications in this context are not yet reported. We present a case with gangrene of the prepuce and focal cutaneous necrosis of the ipsilateral buttock and foot after coil embolization of one IIA. Multiple atheroemboli were found with the histopathologic examination of the excised prepuce. Atheroembolization is a rare complication of therapeutic IIA occlusion, and the ischemic sequels can be severe because of the coincidence of atheroembolization and occlusion of the main supplying artery.

Angiography↗

PubMed2002

The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation.

Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerase negative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.

Antimetabolites, Antineoplastic↗

PubMed2002

Pleomorphic liposarcoma: clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: a study from the French Federation of Cancer Centers Sarcoma Group.

The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.

Adolescent↗