cyclin-d1 and Soft-Tissue-Neoplasms

Superficial CD34-positive fibroblastic tumor (SCPFT) is a fibroblastic/myofibroblastic soft tissue tumor of rarely metastasizing intermediate malignancy. Some recent studies have described a relationship between SCPFT and PRDM10-rearranged soft tissue tumor (PRT) based on SynCAM3 and PRDM10 expression on immunohistochemistry. We performed CD34, cytokeratin AE1/AE3, SynCAM3, and PRDM10 immunohistochemistry in SCPFT and its histological mimics, including myxoinflammatory fibroblastic sarcoma (MIFS), superficially localized myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma. We also examined cyclin D1 expression because it is expressed in MIFS and MFS. We conducted fluorescence in situ hybridization (FISH) of PRDM10 rearrangement in SCPFT cases. On immunohistochemistry, only SCPFT showed strong and diffuse SynCAM3 expression. SCPFT also exhibited strong nuclear and weak cytoplasmic cyclin D1 expression, which was similar to that observed in MIFS. Two of five SCPFT cases exhibited nuclear PRDM10 expression. FISH revealed PRDM10 split signals in 44% and 24% of tumor cells in two SCPFT cases showing nuclear PRDM10 expression on immunohistochemistry, respectively. A minority of non-SCPFT cases showed focal SynCAM3 expression, but a combination of SynCAM3 and cyclin D1 in addition to CD34 and cytokeratin AE1/AE3 may be useful for the differential diagnosis of SCPFT and its histological mimics.

Topics: Biomarkers, Tumor; Cyclin D1; Fibrosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Skin Neoplasms; Soft Tissue Neoplasms

Topics: Cyclin D1; Histiocytosis, Non-Langerhans-Cell; Humans; Skin; Soft Tissue Neoplasms; Xanthogranuloma, Juvenile; Xanthomatosis

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumor with a predilection for the distal extremities and a tendency for local recurrence. Morphologically, MIFS consists of spindle and bizarre epithelioid cells resembling virocytes embedded in a fibrous to myxoid stroma with an abundant inflammatory infiltrate. Importantly, the molecular landscape of MIFS is wide and includes: VGLL3 amplification, BRAF fusion/amplification and OGA/TGFBR3 rearrangements. In this study, we describe a variant of MIFS showing a frequent nodular configuration associated with necrosis and recurrent YAP1::MAML2 fusions. The cohort consisted of 7 patients (4 females and 3 males) ranging in age from 21 to 71 years (median: 47 years). Two tumors (28%) occurred in acral locations while the remaining cases were more widely distributed (thigh, n = 2; arm, n = 1; neck; n = 1; chest-wall, n = 1). Tumor size ranged from 10 to 38 mm (median: 20 mm). Histologically, lesions frequently presented as nodules with central areas of necrosis, and were predominantly composed of sheets of epithelioid cells with large vesicular nuclei and prominent nucleoli (Reed-Sternberg-like cells or virocytes). The stroma was mostly fibrous and showed a polymorphous inflammatory infiltrate. Myxoid stromal changes were focally seen in one case, and pseudolipoblasts were absent. The immunophenotype was nonspecific, with only pan-keratin (AE1-AE3) and cyclin D1 expression in a subset of cases. RNA-Sequencing detected YAP1::MAML2 fusions in 3/7 cases; aCGH showed no significant gene copy number variations in 4 tested cases, and FISH analysis showed no VGLL3 amplification in 1 tested case. Follow-up was available for 6 cases, ranging from 7 to 63 months (median: 42 months). Local recurrence and metastasis were not seen and one tumor showed spontaneous regression following initial biopsy. In conclusion, we describe a novel variant of MIFS with distinctive clinicopathological and molecular features for which we propose the term "nodular necrotizing" MIFS.

Topics: Cyclin D1; DNA Copy Number Variations; Female; Fibrosarcoma; Humans; Keratins; Male; Necrosis; Proto-Oncogene Proteins B-raf; RNA; Skin Neoplasms; Soft Tissue Neoplasms; Trans-Activators; Transcription Factors; YAP-Signaling Proteins

Topics: Aged; Cyclin D1; Dermis; Diagnosis, Differential; Female; Fibrosarcoma; Follow-Up Studies; Forearm; Histiocytoma, Benign Fibrous; Humans; Prognosis; Soft Tissue Neoplasms

Sporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumor of mesenchymal origin. It is characterized by local invasive growth and unpredictable growth behavior. Three distinct mutations involving the CTNNB1 (β-catenin) gene have been identified in the vast majority of DTF tumors, which cause activation of the Wnt signaling pathway and impact prognosis. This study examines whether the different CTNNB1 mutants (T41A, S45F) occurring in DTF tumors differentially affect Wnt signaling activity, which might explain the different disease course between DTF patients harboring different CTNNB1 mutations.. Real-time polymerase chain reaction (RT-PCR) on 61 formalin fixed paraffin embedded DTF samples with known CTNNB1 status was used to measure the relative mRNA expression level of Wnt target genes AXIN2, DKK1 and CCND1. Additionally, publicly available mRNA expression data retrieved from the Gene Expression Omnibus of 128 DTF samples were used for an unsupervised cluster analyses based on the expression of a selection of Wnt targets.. No statistically significant difference in relative expression levels of Wnt target genes AXIN2, DKK1 and CCND1 was identified between either CTNNB1 wild-type, S45F or T41A mutated DTF samples. Moreover, the hierarchical cluster analyses using selected Wnt targets did not discriminate between different CTNNB1 mutation types.. No differences in the expression levels of Wnt target genes were observed between the different CTNNB1 mutation types in DTF tumors. Further studies are needed to decipher the mechanism accounting for the diverse disease courses between DTF patients with different CTNNB1 variants.

Topics: Adolescent; Adult; Aged; Axin Protein; beta Catenin; Child; Child, Preschool; Cyclin D1; Female; Fibromatosis, Abdominal; Fibromatosis, Aggressive; Gene Expression; Humans; Infant; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Mutation; RNA, Messenger; Soft Tissue Neoplasms; Wnt Signaling Pathway; Young Adult

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Topics: beta Catenin; Cyclin D1; Female; Fibrosarcoma; Gene Rearrangement; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Infant, Newborn; Kidney Neoplasms; Male; Nephroma, Mesoblastic; Oncogene Proteins, Fusion; Soft Tissue Neoplasms

We describe 23 cases of high-grade myxoinflammatory fibroblastic sarcoma (MIFS). The patients were 15 women and 8 men, with the age ranging at the time of diagnosis from 39 to 93 years (mean, 64.3 years; median, 66 years). Follow-up was available for 18 patients, of whom 9 developed metastatic disease; 7 of these died. Most tumors showed a predilection for the soft tissues of the extremities, with 14 cases involving the lower limb and 5 the upper extremity. However, in both sites, the acral parts were affected in only 1 case each. Of the 4 remaining tumors, 2 were found in axilla, 1 was found in sacral area, and 1 developed in the scar on the breast, 14 years after previous excision of a mammary carcinoma and subsequent local irradiation. The tumor size ranged from 1.3 cm to as much as 30 cm in the largest dimension with a mean size of 8.3 cm. Histologically, the tumors were characterized by occurrence of 3 types of characteristic cells, including (1) lipoblast-like cells with an ample, distended, mucin-filled cytoplasm compartmentalized by a variable number of intracytoplasmic septa, thus remotely resembling soccer balls; (2) large, polygonal, bizarre ganglion-like cells similar to those seen in the Hodgkin disease, also called Reed-Sternberg-like cells. Within an ample, deeply eosinophilic cytoplasm, there was an oval nucleus with vesicular chromatin and a large, inclusion-like nucleolus. Binucleated, multinucleated, or more pleomorphic forms of these cells were also present; (3) cells with emperipolesis of variable sizes, ranging from very inconspicuous neoplastic cells containing only one to a few engulfed cells to conspicuous large ones having many inflammatory cells, usually polymorphonuclear leukocytes admixed with various numbers of some lymphoid cells, within the cytoplasm. Quite often, we found elements that combined the histologic features of all the above 3 characteristic tumor cell types. In 2 tumors, we found an additional undifferentiated spindle cell sarcoma component, whereas in another tumor, a chondrosarcomatous moiety was evident. For comparison, we studied 10 cases of pleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues. Based on the identification of morphological changes typical for MIFS within most of the cases of PHAT, we suggest that most cases of PHAT represent examples of MIFS merely having hyaline ectatic vessels.

Topics: Adult; Aged; Aged, 80 and over; Chondrosarcoma; Cyclin D1; Female; Fibrosarcoma; Follow-Up Studies; Humans; Hyalin; Immunohistochemistry; Inflammation; Male; Middle Aged; Myxosarcoma; Neoplasm Recurrence, Local; Soft Tissue Neoplasms

The aim of this study was to investigate the expression of cell cycle regulators p53, p16, cyclin-D1, and retinoblastoma (Rb) gene protein in leiomyosarcoma of the peripheral soft in order to identify expression profiles potentially useful for clinical prognostic purposes.. A tissue microarray representing 70 localized leiomyosarcomas of the limbs and limb girdles was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for p53, p16, cyclin-D1, and Rb using standard techniques. Staining was scored as either absent-low (<20% of neoplastic cells) or moderate-diffuse (≥20%). Outcome analysis was performed for local recurrence-free survival (LFS), metastatic disease-free survival (MDFS), and disease-specific survival (DSS).. Kaplan-Meier analysis of survival revealed that no single alteration of the factors examined was associated with outcome, but tumors showing concomitant alteration of p16 and p53 were characterized by reduced MDFS and DSS (P = 0.01 and P < 0.001, respectively). In addition, patients who received adjuvant therapy consisting of radiotherapy alone or radiotherapy and chemotherapy had a better DSS than those receiving surgery alone or surgery and chemotherapy (P = 0.05). In multivariate analysis, altered p16/p53 remained the only parameter predictive of MDFS and DSS (P = 0.048, hazard ratio [HR] = 2.488, 95% confidence interval [95% CI] 1.006-5.116; P = 0.043, HR = 2.498, 95% CI 1.029-5.909, respectively).. Accumulation of cell cycle alterations represents a prognostic indicator in localized soft tissue leiomyosarcoma, and in particular altered p16/p53 expression is associated with an unfavorable prognosis. This may help the clinical management of patients with leiomyosarcomas.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Female; G1 Phase; Humans; Immunoenzyme Techniques; Leiomyosarcoma; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Prognosis; Retinoblastoma Protein; S Phase; Soft Tissue Neoplasms; Tissue Array Analysis; Tumor Suppressor Protein p53

The traditional view that immunoglobulin (Ig) is produced only by B lymphocytes has been challenged, because it has been demonstrated that Ig genes and proteins are expressed in epithelial cancer cells. However, whether Ig expression in nonlymphoid cells is limited to epithelial cells is unclear. Because sarcomas differ distinctly from carcinomas in their biologic and clinical features, the authors investigated the question of nonlymphoid IgG expression in soft tissue lesions.. Immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR) were used to demonstrate IgG expression in 80 soft tissue lesions. The correlation between Ig expression and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and cyclin D1) in sarcomas was investigated by immunohistochemical and statistical analyses.. Igkappa was identified in 97.4% of sarcomas and in 31.7% of benign lesions by immunohistochemistry. The difference was statistically significant (P < .01). Messenger RNA from the IgG1 heavy-chain constant region was also detected by in situ hybridization. Variable-diversity-joining recombination sequences of both heavy and light chains were obtained by PCR and sequencing. Moreover, the labeling index of PCNA, Ki-67, and cyclin D1 was much higher in sarcomas with high Igkappa expression than in sarcomas with low Igkappa expression (P < .01 for PCNA and cyclin D1; P < .001 for Ki-67). There were more grade 3 sarcomas with high Igkappa expression compared with grade 1 and 2 sarcomas (P < .05).. IgG was identified in a wide variety of soft tissue tumors and correlated well with proliferation markers and tumor grades. IgG may be a useful marker for cell proliferation in sarcomas.

Topics: Base Sequence; Biomarkers, Tumor; Cell Proliferation; Cyclin D1; Humans; Immunoglobulin G; Immunoglobulin gamma-Chains; Immunoglobulin Light Chains; Ki-67 Antigen; Molecular Sequence Data; Proliferating Cell Nuclear Antigen; Sarcoma; Soft Tissue Neoplasms; Tumor Suppressor Protein p53

We have studied 11 cases of low-grade fibromyxoid sarcoma (LGFMS) and 15 cases of fibromatosis with respect to clinicopathological features and immunohistochemical expression of Ki-67, nm23, cyclinD1, and p53, in order to investigate the differential diagnosis between this two groups. Formalin-fixed, paraffin-embedded sections from 11 cases of LGFMS and 15 cases of fibromatosis were studied histologically and immunohistochemically. The immunostainings were semiquantitatively evaluated using the Allred score system. Microscopically, LGFMS was composed of bland spindle cells arranged in a whorled pattern showing alternating myxoid zones and fibrous stroma zones with prominent arcade curvilinear capillaries. Cytological atypia, mitotic figures, and tumor necrosis were absent in all 11 cases of LGFMS. In contrast, fibromatosis was less cellular and more fascicular, containing more collagen and showing no alternating fibrous and myxoid zones as compared with LGFMS. The immunostaining scores of nm23 in LGFMS were significantly lower than that in fibromatosis. The immunostaining scores of Ki-67, p53, and cyclinD1 in LGFMS were significantly higher than that in fibromatosis. Thus, we consider that LGFMS can be distinguished from fibromatosis by clinicopathological features, and assessments of the immunohistochemical expression level of cyclinD1, p53, nm23, and Ki-67 are helpful in the differential diagnosis.

Topics: Adolescent; Adult; Aged; Cyclin D1; Diagnosis, Differential; Female; Fibroma; Fibrosarcoma; Humans; Ki-67 Antigen; Male; Middle Aged; Neoplasm Staging; NM23 Nucleoside Diphosphate Kinases; Soft Tissue Neoplasms; Tumor Suppressor Protein p53; Young Adult

Synovial sarcoma (SS) is a highly aggressive soft tissue sarcoma that causes death in more than half of the affected patients. An immunohistochemical and molecular study of the BCL2, MKI67, and CCND1 genes (expressing the BCL2, KI-67, and cyclin D1 proteins, respectively) was performed to determine the expression profiles in correlation with mRNA levels, and to assess the possible utility of these genes as a potential target for the treatment. Cyclin D1 staining was identified in 18 of 30 cases (60%), and CCND1 mRNA was overexpressed in 15 of 32 cases (47%). KI-67 nuclear immunoreactivity was found in 14 of 29 cases (48%), and MKI67 mRNA was overexpressed in 12 of 32 cases (37.5%). The high level of MKI67 mRNA was observed predominantly in monophasic SS. BCL2, a negative regulator of apoptosis, was expressed in all 32 cases. The intensity of the BCL2 protein expression correlated well with the mRNA level (P<0.0001). The high level of BCL2 mRNA correlated with a high level of CCND1 mRNA, but not with MKI67 mRNA level. Despite advances in therapy of sarcomas, the prognosis of patients with SS remains unfavorable, and a search for an improved therapy approach remains necessary. The strong immunopositivity of BCL2 in SS correlates well with a high level of BCL2 mRNA. Treatment with antisense BCL2 (G3139) may therefore represent an appropriate alternative therapy for patients with BCL2-positive synovial sarcomas.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Cell Nucleus; Child; Child, Preschool; Cyclin D1; Female; Humans; Immunohistochemistry; Infant; Ki-67 Antigen; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sarcoma, Synovial; Soft Tissue Neoplasms; Statistics, Nonparametric

The association between aberrant (nuclear) beta-catenin expression and cyclin D1 accumulation has been demonstrated in diverse neoplasms. In synovial sarcoma (SS), aberrant beta-catenin expression has prognostic relevance, but the association with cyclin D1 has not been established. The SYT-SSX fusion protein, unique to SS, may independently increase cyclin D1.. To determine whether nuclear beta-catenin is associated with cyclin D1 overexpression in SS and whether primary and metastatic SS differ in the expression of these markers.. We incorporated 82 tumors initially diagnosed as SS into a tissue array. Fluorescence in situ hybridization with custom probes was used to select t(X;18) positive tumors. Clinical data, tumor type and outcome were tabulated. The tumors were tested for the association between nuclear beta-catenin and cyclin D1 immunostaining. Primary and metastatic tumors were compared.. Fifty-one tumors (41 primary and 10 metastatic) from 43 patients demonstrated t(X;18). Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear beta-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively. No significant difference was noted between primary and metastatic tumors with respect to the above markers. The presence of nuclear beta-catenin showed a significant association with cyclin D1 expression (P < .001). A small number of cyclin D1 cases were negative for nuclear beta-catenin but positive for phosphorylated Akt.. Increased cyclin D1 in SS may be driven by abnormally expressed beta-catenin, similar to other neoplasms. The pattern of expression of these markers is established early during tumorigenesis.

Topics: Adolescent; Adult; Aged; beta Catenin; Biomarkers, Tumor; Cell Nucleus; Chromosomes, Human, Pair 18; Chromosomes, Human, X; Cyclin D1; Extremities; Female; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; Middle Aged; Sarcoma, Synovial; Soft Tissue Neoplasms; Survival Rate; Tissue Array Analysis; Translocation, Genetic

This study was designed to test cyclin D1 as a prognostic marker in patients with soft tissue sarcomas (STS), and to evaluate the usefulness of laparoscopy for determining cyclin D1 overexpression.. The records of 62 patients with STS were collected: 28 with retroperitoneal STS (RSTS) and 34 with extremity STS (ESTS). A total of 51 patients underwent surgical resection, whereas 11 did not undergo surgery because of advanced tumor stage. Preoperative-intraoperative laparoscopic staging was performed for patients judged to be resectable at preoperative imaging.. Cyclin D1 was overexpressed in 30 (58.8%) of 51 resected patients and in 10 (90.9%) of 11 nonresected patients. Laparoscopy avoided unnecessary laparotomy in 9 (32.1%) of 28 RSTS patients.. High tumor grade, positive surgical margins, local recurrence, distant metastases, and cyclin D1 overexpression were related to poor survival. Multivariate analysis demonstrated cyclin D1 to be the only independent factor. Laparoscopy was shown to be useful for avoiding useless laparotomies.

Topics: Biopsy, Needle; Cyclin D1; Female; Humans; Laparoscopy; Male; Middle Aged; Prognosis; Sarcoma; Soft Tissue Neoplasms; Survival Rate

Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited.. To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior.. The p53 and Rb-cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively.. Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse.. Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb-cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.

Topics: Cell Cycle Proteins; Cell Nucleus; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinases; G1 Phase; Humans; Immunohistochemistry; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Retinoblastoma Protein; Sarcoma; Soft Tissue Neoplasms; Tumor Suppressor Protein p53

We previously demonstrated that approximately one-half of soft-tissue sarcomas were devoid of either pRB, the product of the retinoblastoma gene, or 16, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal tumors without metastatic potential did not express RB by immunohistochemistry. We now studied the expression of two additional important cell-cycle regulators, namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In the aggregate, our data provide a comprehensive overview of the importance of cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining data were correlated with expression of pRB and p15 and with a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no correlation between expression of these two genes and histologic tumor type or grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually exclusive events. Considering all four cell-cycle regulators, sarcomas had a significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas but 39% of STT-LMP showed normal expression of all four gene products. Based on our findings, overexpression of cyclin D1 and (presumably mutant) p53 appear to be among the most common molecular alterations in human mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the great majority of sarcomas; it is present significantly less frequently in low-grade lesions.

Topics: Cell Cycle; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Mesoderm; Mutation; Neoplasm Proteins; Retinoblastoma Protein; Sarcoma; Soft Tissue Neoplasms; Tumor Suppressor Protein p53

Solitary fibrous tumors (SFTs) are infrequent soft tissue neoplasms which are usually benign and surgically curable. However, their behavior is not always predictable, although several clinical and pathological criteria of malignancy have been established. In many cancers, including some soft tissue tumors, telomerase activity (TA) has been shown to be a new reliable pathological marker of malignancy. Overexpression of some cyclins is associated with higher degrees of malignancy and predictive of the clinical course. In this study, we evaluated TA, mitotic and apoptotic indices (MI, AI), and the expression of Ki-67, cyclins D1 and A in five typical and two clinicopathologically atypical SFTs, the latter two of which had also recurred. High TA was demonstrated in the two atypical cases, which also showed a higher labeling index to Ki-67, as well as higher cyclin D1 and A expression, and either none or very few apoptoses. We suggest that TA, Ki-67, cyclin expression, and AI be evaluated in SFTs as possible adjunctive pathological criteria of behavior.

Topics: Adult; Apoptosis; Cyclin A; Cyclin D1; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Neoplasms, Fibrous Tissue; Prognosis; Soft Tissue Neoplasms; Telomerase

Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma cells, and lymphocytes. Cytokines are possibly involved in its pathogenesis. Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins. A combination of nested PCR with several negative controls and Southern blot methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally, strong expression was demonstrated by in situ hybridization in many tumoral nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for human IL-6 and cyclin D1. These cytokines probably have a paracrine action and may sustain myofibroblastic growth. HHV-8 could play an essential role in triggering IMT development by a local reactivation of viral lytic replication. The relationship between HHV-8 and immunosuppression status as the only associated cause for tumorigenesis should be revised.

Topics: Adult; Aged; Cyclin D1; DNA, Viral; Female; Granuloma, Plasma Cell; Herpesvirus 8, Human; Humans; Interleukin-6; Leg; Lung Neoplasms; Lymph Nodes; Lymphatic Diseases; Male; Middle Aged; Soft Tissue Neoplasms

Epithelioid sarcoma is a distinctive, rare soft tissue sarcoma that typically involves the distal extremities in young adults, and shows epithelioid morphology and immunohistochemical markers of epithelial differentiation. The genetic background of epithelioid sarcoma is poorly understood, and knowledge of it could give insights into the pathogenesis of this tumor and its possible relationship with other malignant tumors. In this study, we analyzed DNA copy number changes in 30 epithelioid sarcomas by comparative genomic hybridization. DNA was extracted from microdissected samples of formaldehyde-fixed and paraffin-embedded tumors with a minimum of 60% of tumor cells in each sample. Sixteen tumors (53%) showed DNA copy number changes at one to six different genomic sites. The majority of the changes were gains, seen in 14 tumors, whereas 10 tumors showed losses. The most common recurrent gains were at 11q13 (five cases), 1q21-q23 (four cases), 6p21.3 (three cases), and 9q31-qter (three cases). High-level amplifications were detected once in 6p21.3-p21.1 and once in 9q32-qter. Recurrent losses were seen at 9pter-p23 (three cases), 13q22-q32 (three cases), 1p13-p22 (two cases), 3p12-p14 (two cases), 4q13-q33 (two cases), 9p21 (two cases), and 13q32-qter (two cases). The most common recurrent gain at 11q13 was seen in both classic cases and angiomatoid and rhabdoid variants supporting the relationship of these variants with the classic epithelioid sarcoma. Expression of cyclin D1 gene, located in 11q13, was immunohistochemically detected in nine of 15 cases including three of five cases with gain of 11q13, suggesting its involvement in epithelioid sarcoma. The observed comparative genomic hybridization changes give targets for future genetic studies on epithelioid sarcoma.

Topics: Adolescent; Adult; Cell Nucleus; Cyclin D1; DNA, Neoplasm; Female; Gene Dosage; Humans; Image Processing, Computer-Assisted; In Situ Hybridization, Fluorescence; Karyotyping; Male; Middle Aged; Sarcoma; Soft Tissue Neoplasms; Survival Rate