Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor

Kawai, Akira; Noguchi, Masayuki; Beppu, Yasuo; Yokoyama, Ryohei; Mukai, Kiyoshi; Hirohashi, Setsuo; Inoue, Hajime; Fukuma, H

doi:10.1002/1097-0142(19940515)73:10<2499::aid-cncr2820731008>3.0.co;2-g

Cited by 110 publications

(66 citation statements)

References 19 publications

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“…p53 immunopositivity has been previously shown to correlate with soft tissue sarcoma outcome. 7,8 Current soft tissue sarcoma prognostic staging systems are based on crude clinical and tumor variables such as size, grade, and the presence or absence of overt regional nodal or distant visceral metastasis. There is a growing awareness that more sensitive prognostication and therapeutic decision-making algorithms will need to incorporate relevant molecular determinants.…”

Section: Discussionmentioning

confidence: 99%

“…5 Such mutations are found more fre-quently in metastases than in primary tumors and in high-grade versus low-grade sarcomas, and these mutations are thought to have a significant negative impact on both overall as well as sarcoma-specific survival. [6][7][8] Our own investigations of autologous human primary and metastatic sarcoma have demonstrated that clonal expansion of p53-mutated cells in soft tissue sarcoma confers distinct metastatic advantages. 9 Moreover, we have shown that reintroduction of wtp53 into soft tissue sarcoma cells that harbor a p53 mutation inhibits cell proliferation, soft agar colony formation in vitro, and tumorigenesis in severe combined immunodeficient (SCID) mice.…”

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confidence: 99%

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High prevalence of p53 exon 4 mutations in soft tissue sarcoma

Das

Kotilingam

Korchin

et al. 2007

Cancer

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Objective The contribution of genetics to osteoarthritis (OA) progression is not known. To gain more insight into whether familial factors play a role in disease progression of OA, we analyzed familial aggregation of radiologic OA progression in a study of sibling pairs (the Genetics, Arthrosis, and Progression [GARP] study). Methods A total of 105 white probands and their 105 siblings with OA at multiple joint sites were included in a prospective cohort study. Radiologic progression of OA was defined as a 1‐point score increase in total scores for severity of joint space narrowing (JSN) or osteophytes on standardized radiographs of the hands, knees, and hips obtained at baseline and after 2 years. Odds ratios were calculated for siblings and probands sharing radiologic disease progression. Results A total of 100 probands and 93 siblings were followed for 2 years (median age 60 years, 80% women). In 92 sibling pairs both the proband and sibling had complete radiographic followup. Radiologic progression of JSN and osteophytes was present in 47% and 42% of the probands and 34% and 37% of the siblings, respectively. The odds ratios (95% confidence intervals), adjusted for age, sex, and body mass index, of a sibling having radiologic progression if the proband had progression were 3.0 (1.2–7.8) for JSN progression and 1.5 (0.6–3.6) for osteophyte progression. A dose‐response relationship was found between the amount of increase in JSN total scores among probands and the progression of JSN in siblings. Conclusion Familial factors played a role in the radiologic progression of JSN over 2 years in patients with OA at multiple sites.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

High prevalence of p53 exon 4 mutations in soft tissue sarcoma

Das

Kotilingam

Korchin

et al. 2007

Cancer

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“…27 The percentage of patients with positive immunoreactions of p53 was high in those with malignant schwannoma (100%). 28 The local recurrence, nuclear pleomorphism, and especially the high percentage of positive cells with p53 (80%) and Ki-67 (30%) antibodies support the aggressive nature of the lesion. 29 Neurofibromas and schwannomas displayed similar courses, but the clinical features of typical and cellular tumors were not the same.…”

Section: Discussionmentioning

confidence: 93%

Malignant Transformation of Benign Intraosseous Schwannoma in the Cervical Spine: A Case Report with an Immunohistochemical Study

Peng

Chen

et al. 2011

International Surgery

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Although 3% to 30% of lesions in von Recklinghausen disease undergo malignant transformation, malignant transformation of benign solitary schwannoma is extremely rare. We reported a case of recurrence and malignant transformation in a benign intraosseous schwannoma arising in the cervical spine of a 44-year-old man. The patient presented giant tumor in the C3 vertebral body with aggressive, expansile, and osteolytic destruction and relapsed 2 years after surgical resection and spinal reconstruction. Clinical data, radiologic characteristics, surgical management, histopathologic and immunohistochemical features were noted in the duration of follow-up. The local recurrence, nuclear pleomorphism, epithelioid differentiation, a small number of positive S-100 protein-staining cells, and especially the high percentage of positive cells with p53 (80%) and proteins support the aggressive nature of the lesion in malignant transformation of benign intraosseous schwannoma in the cervical spine. Immunohistochemistry would be useful as an ancillary technique in diagnosis. It is our practice to suggest that such case has to be carefully resected and the patient followed up. An intraosseous schwannoma is the infrequent occurrence and uncommon lesion. The mandible is the most common site. 6 The incidence of the intraosseous schwannomas is less than 0.2% in primary bone tumors.7 Cases of the osseous changes in the spinal schwannomas are observed in almost one third of cases (6 of 17) where, radiographically, 1 or 2 vertebral bodies can be seen eroded with welldefined marginal sclerosis. 4 The most common imaging findings of extradural spinal schwannomas involving bone include pedicle erosion, vertebral body scalloping, and widening of the neural foramen.8 Based on the radiologic findings, Sridhar et al 9 proposed a classification system of spinal schwannomas as types I to V, in which type V of spinal schwannomas was defined as a giant invasive tumor in spinal intraosseous schwannomas. In a few patients the tumor presents as an expansile vertebral body lesion in the cervical spine, as reported in the literature. 6,[9][10][11][12] Although primary malignant peripheral nerve sheath tumors (MPNSTs) of spine with or without the intraosseous involvement in association with von Recklinghausen's disease (neurofibromatosis type I) have been reported in the thoracic and lumbar spine, 12-15 malignant transformation of benign solitary schwannoma is extremely rare. 16,17 Woodruff et al 17 described 2 patients with such changes involving a finger and pelvis and reviewed 7 patients with malignant transformation. Malignant transformation of benign schwannoma has also been occurred in the vestibular nerve, 18 retropharyngeal space, 19 neck, 20 and intrathoracic extrapleural space 21 without an association of von Recklinghausen disease. The possibility of occult malignancy could also be associated with a previous radiation.18,22 To our knowledge, malignant transformation of benign intraosseous schwannomas in the spine has not been reported yet.W...

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“…Accordingly, the p14 ARF -p53 pathway may contribute to the presence of the round cell component and malignant progression in this tumor. (16) In several kinds of STS, nuclear overexpression of p53 protein (11) and mutation of the p53 gene (12) have been reported as poor prognostic factors. As for MDM2 alterations, overexpression (4,5) , low proliferative rate (6) …”

Section: Ink4amentioning

confidence: 99%

“…Synovial sarcoma RT-PCR Poor prognosis (7) , high proliferative rate (8) PAX3-FKHR Alveolar RMS RT-PCR Poor prognosis (2) Tumor-suppressor genes p53 and MDM2 coexpression Mixed STS IHC Poor prognosis (9) Dedifferentiated LS IHC Dedifferentiation (10) p53 Mixed STS IHC Poor prognosis (11) Mixed STS Mutation Poor prognosis (12) Leiomyosarcoma IHC, mutation Poor prognosis in deep tumor (13) Synovial sarcoma IHC Poor prognosis (14) Myxoid/round cell LS IHC Poor prognosis (15) Myxoid/round cell LS IHC, mutation High histological grade, poor prognosis (16) ES/PNET IHC Poor prognosis (17) DFSP Mutation Malignant transformation to fibrosarcoma (18) MDM2 mRNA Mixed STS qRT-PCR Poor prognosis (19) p16 INK4a Leiomyosarcoma IHC Poor prognosis (20) p14 ARF Myxoid/round cell LS IHC Poor prognosis (16) RB Dedifferentiated LS IHC, LOH, mutation Dedifferentiation (21) DAP kinase, p53 Leiomyosarcoma MSP, mutation High histological grade, poor prognosis (22) RASSF1A Mixed STS MSP Poor prognosis, frequent in leiomyosarcoma (23) Cell cycle regulators CHFR MPNST IHC Poor prognosis (24) p21 WAF1 Myxofibrosarcoma IHC High histological grade, poor prognosis (25) Growth factors and receptors EGFR Mixed STS IHC Poor prognosis (26) HGF/MET coexpression Synovial sarcoma IHC Poor prognosis (27) Multidrug resistance P-glycoprotein Mixed STS IHC Poor prognosis (28) Mixed STS IHC Poor response to chemotherapy (29) Mixed STS IHC Large tumor size, high stage (30) MDR1/MRP1, coexpression…”

Section: Ss18-ssx1mentioning

confidence: 99%

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Oda

Tsuneyoshi

2009

Cancer Science

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In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18-SSX, EWS-FLI1, and PAX3-FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1 tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200-208) S oft tissue sarcomas are relatively rare malignant neoplasms compared with carcinomas and other neoplasms, and they constitute less than 1% of all cancers. STS are composed of many histological subtypes, such as pleomorphic undifferentiated sarcoma or malignant fibrous histiocytoma, leiomayosarcoma, and liposarcoma. In addition to their wide variety of subtypes, it is often difficult to make an accurate histological diagnosis because certain kinds of STS share similar morphological features. However, it is important to make a definitive diagnosis so that adequate therapy can be administered in each case. Recently, several reciprocal chromosomal translocations and fusion transcripts have been proven to be characteristic of particular histological types (Table 1; Fig. 1). The detection of these fusion transcripts is useful for the differential diagnosis of histologically peculiar cases.In relapsed cases of STS complete remission is difficult, despite the conventional multidisciplinary therapy. Therefore, novel therapies such as molecular target therapy are required, especially in relapsed cases. Several investigators have analyzed tumor-...

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Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor

Cited by 110 publications

References 19 publications

High prevalence of p53 exon 4 mutations in soft tissue sarcoma

High prevalence of p53 exon 4 mutations in soft tissue sarcoma

Malignant Transformation of Benign Intraosseous Schwannoma in the Cervical Spine: A Case Report with an Immunohistochemical Study

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

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