Publications by authors named "Manuela Pelmus"

17 Publications

  • Page 1 of 1

Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Sci Rep 2020 09 7;10(1):14704. Epub 2020 Sep 7.

Lady Davis Institute, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline. Mutant allele frequency at baseline was associated with clinical characteristics. Levels drastically fell after one cycle of NAC, especially in patients whose tumors would go on to have a pathological complete response (pCR), but then rose significantly before surgery in patients with significant residual tumor at surgery (p = 0.0001). The detection of ctDNA early during treatment and also late at the end of NAC before surgery was strongly predictive of residual tumor at surgery, but its absence was less predictive of pCR, especially when only TP53 variants are considered. ctDNA detection at the end of neoadjuvant chemotherapy indicated significantly worse relapse-free survival (HR = 0.29 (95% CI 0.08-0.98), p = 0.046), and overall survival (HR = 0.27 95% CI 0.075-0.96), p = 0.043). Hence, individualized multi-variant ctDNA testing during and after NAC prior to surgery has prognostic and predictive value in early TNBC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-71236-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477566PMC
September 2020

Targeted sequencing of histologically defined serous endometrial cancer reflects prognosis and correlates with preoperative biopsy.

Gynecol Oncol Rep 2019 Nov 27;30:100521. Epub 2019 Nov 27.

Division of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.

The aim of this study was to evaluate the impact of discordant endometrial sampling on the prognosis of patients finally diagnosed with uterine papillary serous carcinoma (UPSC) and to analyze UPSC mutational profile. Retrospective cohort study comparing outcomes of patients post-operatively diagnosed with UPSC and preoperatively diagnosed with endometrioid endometrial cancer (EEC) or UPSC. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 40 patients post-operatively diagnosed with UPSC, using next generation sequencing. 61 patients with UPSC on post-surgical, final pathology were included in the study. Prior to surgery, 15 were diagnosed with EEC (discordant) and 46 were correctly diagnosed with UPSC (concordant). After a median follow-up of 41.6 months [5.4-106.7], a preoperative diagnosis of EEC was associated with better 3-year progression-free survival (100% vs. 60.9%, P = 0.003) and longer disease free interval (63.5 versus 15 months, P = 0.026) compared to patients with an initial diagnosis of UPSC. Patients with a concordant diagnosis of UPSC were 5 times more likely to progress or die compared to those with a discordant EEC diagnosis (P = 0.02, P = 0.03, respectively), and their tumors were associated with higher rates of TP53 (88.9% vs. 61.5%, P = 0.04), and a lower rate of PTEN (14.8% vs. 38.5%, P = 0.09) and ARID1A (3.7% vs. 23.1%, P = 0.05) mutations. A pre-surgical diagnosis of EEC is associated with improved prognosis in patients with UPSC. Some histologically defined UPSC tumors contain endometrioid-like molecular characteristics that may confer a survival advantage, suggesting a possible need for molecular approaches to better stratify patients into risk groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gore.2019.100521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906727PMC
November 2019

Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors.

Gynecol Oncol Rep 2018 May 19;24:43-47. Epub 2018 Mar 19.

Division of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2, Canada.

Objective: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC).

Methods: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing.

Results: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%,  = .03; distant: 50% vs. 17.5%,  = .004) and progression events (73.1% vs. 26.3%,  < .001), with shorter mean progression-free survival (16 months compared to 26.5 months,  < .01). In a multivariate analysis, LUSI was the only significant pathological factor, associated with a 2.9-fold increase in the risk of progression ( = .007), and a 2.6-fold increase in the risk of death ( = .02). In the subgroup of patients with UPSC, mutations were identified in 54 genes, including (80%), (40%), and (22.5%). Frequent mutations in the PTEN-PI3K-AKT signaling pathway were found in patients with tumor in the upper uterine segment only ( = .04), with being mutated in 29% of the samples ( = .07).

Conclusion: Type II endometrial cancers presenting in the LUS have a significantly worse prognosis and this might be associated with a unique mutational profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gore.2018.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003406PMC
May 2018

Distinct homologous recombination gene expression profiles after neoadjuvant chemotherapy associated with clinical outcome in patients with ovarian cancer.

Gynecol Oncol 2018 03 1;148(3):553-558. Epub 2018 Feb 1.

Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada. Electronic address:

Objective: The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens.

Study Design: RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival.

Results: In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively.

Conclusion: Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2018.01.017DOI Listing
March 2018

The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience.

Mod Pathol 2017 11 28;30(11):1567-1576. Epub 2017 Jul 28.

Department of Oncology, Lady Davis Institute, McGill University, Montreal, QC, Canada.

One of the major challenges in biomarker development is the collection of tumor tissue of adequate quality for analysis. A prospective clinical trial was initiated to collect tissues from triple negative breast cancers prior to and after neoadjuvant chemotherapy in order to study the mechanisms of chemoresistance. Sixty patients had pre-chemotherapy biopsies performed by either a surgeon or a radiologist, while those with residual tumor after chemotherapy had research-only biopsies and/or surgical samples collected in liquid nitrogen, RNA-later and formalin. We examined each core for tumor cellularity, stromal content, and necrosis after which, RNA and DNA extraction was performed. We found that biopsies collected with ultrasound guidance were more likely to contain tumor than those collected by the surgeon. Patient reluctance to undergo research-only biopsies after chemotherapy was not a problem. Pre-chemotherapy tumor biopsies frequently did not contain any tumor cells (15%) or did not have ≥50% tumor content (63%). Indeed, 50% of patients had at least 2 pre-chemotherapy core biopsies with <50% tumor content. After chemotherapy, 30% of biopsy or surgical samples in patients with incomplete response did not contain any tumor. Finally, RNA-later not only made histopathological assessment of tumor content difficult, but yielded less DNA than fresh snap frozen samples. We recommend that high-quality tissue procurement can be best accomplished if at least three image-guided core biopsies be obtained per sample, each of these cores be examined for tumor cellularity and that at least some of them be freshly snap frozen in liquid nitrogen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2017.82DOI Listing
November 2017

Breast Tumor Resembling Tall Cell Variant of Papillary Thyroid Carcinoma: A Solid Papillary Neoplasm With Characteristic Immunohistochemical Profile and Few Recurrent Mutations.

Am J Clin Pathol 2017 Apr;147(4):399-410

University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, PA.

Objectives: Breast tumor resembling tall cell variant of papillary thyroid carcinoma (BTRPTC) is a rare breast lesion that is unrelated to thyroid carcinoma. Morphologically, it shows a solid papillary lesion with bland cytology, eosinophilic/amphophilic secretions, nuclear grooves, reversal of nuclear polarity (recently described), and nuclear inclusions. Clinical course is often uneventful with few exceptions reported in the literature. Herein, we report three additional cases.

Methods: Immunohistochemical staining and next-generation sequencing was performed on all three cases.

Results: The lesional cells on all cases were positive for cytokeratin 5 and S100, with weak expression/lack of estrogen receptor. No staining was observed for myoepithelial markers (p63 and myosin heavy chain) around the lesion. IDH2 mutations were identified in two cases at nucleotide 172 (cases 1 and 3). ATM gene mutation was identified in cases 2 and 3 and PIK3CA mutation in case 3. All patients are currently without disease.

Conclusions: BTRPTC is a slow-growing neoplastic lesion that needs to be distinguished from other papillary lesions for optimizing therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqx016DOI Listing
April 2017

Impact of sentinel lymph node mapping on recurrence patterns in endometrial cancer.

Gynecol Oncol 2017 03 16;144(3):503-509. Epub 2017 Jan 16.

Division of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, Quebec H2T 1E2, Canada. Electronic address:

Background: Sentinel lymph node (SLN) mapping has emerged as a promising solution to the ongoing debate regarding lymphadenectomy in the initial surgical management of endometrial cancer. Currently, little is known about its possible impact on location of disease recurrence compared to systematic lymphadenectomy.

Methods: In this retrospective study, 472 consecutive patients with endometrial cancer who underwent either SLN mapping (SLN cohort, n=275) or systematic lymphadenectomy (LND cohort, n=197) from sequential, non-overlapping historical time points were compared. Clinical characteristics were extracted from a prospectively gathered electronic database. Both overall and pelvic sidewall recurrence free survival (RFS) were evaluated at 48-month post-operative follow-up.

Results: No significant difference in overall RFS could be identified between the cohorts at 48months (HR 0.74, 95% CI 0.43-1.28, p=0.29). However, the SLN cohort had improved pelvic sidewall RFS compared to the LND cohort (HR 0.32, 95% CI 0.14-0.74, p=0.007). The pelvic sidewall recurrences accounted for 30% of recurrences in the SLN cohort (8 out of 26 recurrences) compared to 71.4% in the LND cohort (20 out of 28 recurrences).

Conclusions: SLN mapping may enable more efficient detection of the LNs at greatest risk of metastasis and help to guide adjuvant therapy, which in turn seems to decrease the risk of pelvic sidewall recurrences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2017.01.013DOI Listing
March 2017

Complete response and long-term survival of leptomeningeal carcinomatosis from breast cancer with maintenance endocrine therapy.

BMJ Case Rep 2016 Jun 2;2016. Epub 2016 Jun 2.

Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

Leptomeningeal carcinomatosis carries a poor prognosis in breast cancer. Treatment modalities are geared towards tumour molecular characteristics, as well as symptoms and patient performance status. It has previously been postulated that endocrine treatments used for the treatment of metastatic breast cancer do cross the blood-brain barrier and can achieve antineoplastic effects in the central nervous system. We report a case of metastatic breast cancer in a 65-year-old woman who developed leptomeningeal carcinomatosis. She was initially treated with intrathecal methotrexate, which was stopped due to toxicity, followed by maintenance endocrine therapy. She achieved a sustained complete radiological and cerebrospinal fluid cytological response for over 9 years. She eventually passed away of ischaemic bowel unrelated to her cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2016-215525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904438PMC
June 2016

Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors.

BMC Med 2015 Sep 9;13:217. Epub 2015 Sep 9.

Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Côte Ste, Catherine Road, Montréal, QC, H3T 1E2, Canada.

Background: PARP inhibitors have shown promising clinical results in cancer patients carrying BRCA1/2 mutations. Their clinical efficacy could logically be influenced by PARP1 protein levels in patient tumors.

Methods: We screened three cohorts of patients with ovarian cancer, totaling 313 samples, and evaluated PARP1 protein expression by immunohistochemistry with further validation by western blotting.

Results: We observed that up to 60 % of tumors showed little PARP1 protein expression. In serous ovarian tumors, comparing intratumoral PARP1 expression between chemo-naïve and post-chemotherapy patients revealed a decrease in intratumoral PARP1 following chemotherapy in all three cohorts (immunohistochemistry: p < 0.001, n = 239; western blot: p = 0.012, n = 74). The findings were further confirmed in a selection of matched samples from the same patients before and after chemotherapy.

Conclusion: Our data suggest that patients should be screened for PARP1 expression prior to therapy with PARP inhibitors. Further, the observed reduction of intratumoral PARP1 post-chemotherapy suggests that treating chemo-naïve patients with PARP inhibitors prior to the administration of chemotherapy, or concurrently, might increase the responsiveness to PARP1 inhibition. Thus, a change in the timing of PARP inhibitor administration may be warranted for future clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12916-015-0454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565010PMC
September 2015

Metallosis-induced iliopsoas bursal cyst causing venous obstruction and lower-limb swelling after metal-on-metal THA.

Orthopedics 2012 Dec;35(12):e1811-4

Arthroplasty Division, Department of Orthopedic Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

The formation of iliopsoas bursal cystic lesions after total hip arthroplasty is an infrequently reported condition. This article describes an unusual complication of a current-generation metal-on-metal total hip arthroplasty.A woman presented with unilateral spontaneous lower-limb swelling that developed 5 years postoperatively. It occurred secondary to venous obstruction by a metallosis-induced iliopsoas bursal cyst associated with markedly elevated intralesional cobalt and chromium levels. Metal artifact reduction sequence magnetic resonance imaging showed that the bursal cyst was communicating with the hip joint and that it severely compressed the common femoral vein. Based on the findings of high local tissue metal ions and vertical cup positioning causing edge loading, the authors proposed an inflammatory reaction to metal debris that tracked into the iliopsoas bursa and formed a cyst. The patient underwent revision of the excessively vertical acetabular component and conversion to a ceramic-on-ceramic bearing interface, drainage of the bursal cyst, and synovectomy. No signs existed of local recurrence at 1-year follow-up.To the authors' knowledge, the occurrence of metallosis-induced iliopsoas bursitis with secondary pressure effects after contemporary metal-on-metal total hip arthroplasty has not been reported. When treating hip dysplasia, one must avoid maximizing cup-host bone contact at the risk of oververticalization. Iliopsoas bursal cystic lesions can lead to severe vascular compressive symptoms with no ominous radiographic findings. Physicians and orthopedic surgeons should be aware of the possibility of this complication in patients with unexplained unilateral lower-limb swelling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/01477447-20121120-30DOI Listing
December 2012

Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study.

Gynecol Oncol 2012 Nov 19;127(2):332-7. Epub 2012 Aug 19.

Division of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, QC, Canada.

Objective: The objective of this study is to evaluate the detection rate and diagnostic accuracy of sentinel lymph node (SLN) mapping using intra-operative cervical injection of filtered 99mTc-sulfur colloid (99mTc-SC) and patent blue in patients with endometrial cancer.

Methods: Prospective evaluation of the first 100 endometrial cancer patients undergoing SLN mapping using cervical injection of patent blue combined with filtered 99mTc-SC in the operating room was done. Patients underwent robotic-assisted lymphatic mapping with frozen section, hysterectomy, BSO, and completion bilateral lymphadenectomy (including para-aortic nodes in grade 2 and 3 tumors).

Results: At least one SLN was detected in 92% of patients; in 66 of these (72%) bilateral SLN were detected, and in 15 cases the SLN was in the para-aortic area. Eleven percent of all patients had lymph node metastases, and 4 of which had pre-operative grade 1 tumor. The SLN was the only positive node in 44% of the cases with positive nodes. Sensitivity was 89% with 1 false negative result, yielding a negative predictive value of 99% (95% CI 93-100). Specificity was 100% (95% CI 94-100), and positive predictive value was 100% (95% CI 60-100). No complications or anaphylactic reactions were noted.

Conclusions: Intra-operative SLN biopsy, using cervical injection of patent blue and filtered 99mTc-SC in endometrial cancer patients is feasible and yields adequate detection rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2012.08.018DOI Listing
November 2012

Prognostic factors in early-stage leiomyosarcoma of the uterus.

Int J Gynecol Cancer 2009 Apr;19(3):385-90

Department of Pathology, University Hospital of Sherbrooke, Quebec, Canada.

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/IGC.0b013e3181a1bfbcDOI Listing
April 2009

Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increases in tumor necrosis factor-alpha converting enzyme/ADAM17 expression by synovial cells.

J Biol Chem 2007 Nov 19;282(46):33714-33724. Epub 2007 Sep 19.

Immunology Division, Departments of Pediatrics. Electronic address:

Chronic hypoxia and inflammatory cytokines are hallmarks of inflammatory joint diseases like rheumatoid arthritis (RA), suggesting a link between this microenvironment and central pathological events. Because TACE/ADAM17 is the predominant protease catalyzing the release of tumor necrosis factor alpha (TNFalpha), a cytokine that triggers a cascade of events leading to RA, we examined the regulation of this metalloprotease in response to hypoxia and TNFalpha itself. We report that low oxygen concentrations and TNFalpha enhance TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible factor-1 (HIF-1) to the 5' promoter region. This is associated with elevated TACE activity as shown by the increase in TNFalpha shedding rate. By the use of HIF-1-deficient cells and by obliterating NF-kappaB activation, it was determined that the hypoxic TACE response is mediated by HIF-1 signaling, whereas the regulation by TNFalpha also requires NF-kappaB activation. As a support for the in vivo relevance of the HIF-1 axis for TACE regulation, immunohistological analysis of TACE and HIF-1 expression in RA synovium indicates that TACE is up-regulated in both fibroblast- and macrophage-like synovial cells where it localizes with elevated expression of both HIF-1 and TNFalpha. These findings suggest a mechanism by which TACE is increased in RA-affected joints. They also provide novel mechanistic clues on the influence of the hypoxic and inflammatory microenvironment on joint diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M704041200DOI Listing
November 2007

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

Cancer 2003 Dec;98(12):2700-7

Department of Pathology, Bergonié Institute, Bordeaux, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.11840DOI Listing
December 2003

Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases.

Am J Surg Pathol 2002 Nov;26(11):1434-40

Bergonié Institute, Bordeaux, France.

Diagnosing monophasic fibrous and poorly differentiated synovial sarcoma (SS) on morphology alone is often a source of problems for pathologists. SS bear the t(X;18)(p11.2,q11.2) translocation, which proved to be specific for this tumor type and is currently considered one of the most reliable diagnostic criteria. To evaluate the sensitivity of immunohistochemical techniques in diagnosing monophasic fibrous SS (MFSS) and poorly differentiated SS (PDSS), we examined 60 t(X;18)(SYT-SSX)-positive cases (47 MFSS and 13 PDSS) for cytokeratin AE1/AE3, cytokeratin KL1, epithelial membrane antigen, E-cadherin, CD34, S-100 protein, alpha-smooth muscle actin, desmin, h-caldesmon, CD99, bcl2, and C-kit (CD117) antibodies. Of the four epithelial markers tested, epithelial membrane antigen proved to be the most sensitive, reacting with 100% of MFSS and 92% of PDSS, followed by cytokeratin AE1/AE3 (70% of MFSS, 46% of PDSS), cytokeratin KL1 (49% of MFSS, 38% of PDSS), and E-cadherin (47% of MFSS, 54% of PDSS). A staining for cytokeratin AE1/AE3 and/or E-cadherin was observed in 79% of MFSS and 69% of PDSS, and a staining for cytokeratin KL1 and/or E-cadherin was observed in 74% of MFSS and 62% of PDSS. S-100 protein was positive in 38% of MFSS and 23% of PDSS, and alpha-smooth muscle actin in 21% of MFSS and 8% of PDSS. Tumor cells were rarely positive for CD34 (6% of MFSS, 0% of PDSS) and desmin (2% of MFSS, 0% of PDSS). Most SS were strongly positive for bcl-2 (91% of MFSS, 92% of PDSS) and CD99 (91% of MFSS, 100% of PDSS). A weak and focal cytoplasmic reactivity for CD117 was observed in 11% of MFSS (only one case had a strong immunoreactivity) and 8% of PDSS. Staining with h-caldesmon was consistently negative. In conclusion, in keeping with literature data, our results show that reactivity for epithelial membrane antigen, cytokeratin AE1/AE3, and E-cadherin, in combination with CD34 negativity, are the most useful and sensitive markers for diagnosing monophasic fibrous and poorly differentiated t(X;18)-positive SS. They also support the fact that about one third of MFSS and one fourth of PDSS are positive for S-100 protein, a finding of diagnostic relevance when considering their distinction from other spindle to round cell sarcomas, especially malignant peripheral nerve sheath tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00000478-200211000-00005DOI Listing
November 2002