Immunohistochemical Detection of bcl-2 and p53 Proteins and Apoptosis in Soft Tissue Sarcoma: Their Correlations with Prognosis

Abstract

Information on prognostic factors is essential to establish appropriate therapeutic modalities for soft tissue sarcoma (STS). To evaluate the biological nature and prognostic factors of STS, p53 and bcl-2 expression was immuno-histochemically studied on paraffin-embedded sections from 70 patients with STS in the extremities and trunk. In addition, the degree of apoptosis was examined by in situ end-labeling. Histologic diagnoses in these cases were malignant fibrous histiocytoma in 29 cases, liposarcoma in 11, synovial sarcoma in 11, leiomyosarcoma in 5, malignant neurogenic tumor in 5, and others in 9. Tumor cells in 31 of 70 cases (44%) showed positive nuclear staining for p53 protein. There was no correlation between p53 expression and tumor size, histologic grade, argyrophilic nucleolar organizer region (AgNOR) count, cellularity and extent of necrosis. Expression of p53 did not correlate with survival of patients. Tumor cells in 24 of 56 cases (43%) were positive for bcl-2 protein expression. The frequency of bcl-2 expression in the tumor cells showed a direct proportion to tumor size (≥10 vs. < 10 cm) but inverse proportion to AgNOR counts and cellularity. The 5-year survival rate in patients with bcl-2-positive tumors (87%) was more favorable than in those with bcl-2-negative tumors (53%; p < 0.05). The frequency of apoptosis in low-grade STS was significantly higher than that in the intermediate and high-grade STS (p < 0.001). Extent of necrosis, a well-known prognostic indicator in STS, was not correlated with the frequency of apoptosis. Multivariate analysis showed that cellularity, bcl-2, and AgNOR counts were independent prognostic factors in patients with STS. The current study revealed that STS with a higher expression of bcl-2 had lower proliferative activity and larger size than those without. Immunohistochemical detection of bcl-2 is useful for predicting prognosis in patients with STS.

Prognostic factors in soft tissue sarcomaTissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence

“…However, the great number of studies that have been performed without reaching an answer as to a prognostic role of p53 in STS indicate that a possible prognostic importance of p53 immunostaining is small. The transcription regulators Rb and Bcl-2 also interact with p53 function and it is possible that combined alterations in these pathways may be of prognostic importance [36,113,116,122,185].…”

Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus

“…The bcl-2 protooncogene encodes a 26 kDa protein mainly localized in mitochondrial membranes and this bcl-2 protein has been shown to prolong cell survival by inhibiting the apoptotic processes induced by many anticancer drugs, radiation and DNA-damaging agents, processes that are mediated by p53 (Hockenbery et al, 1990;Sentman et al, 1991;Korsmeyer et al, 1992;Miyashita et al, 1993;Wang et al, 1993). bcl-2 expression has been demonstrated in a variety of human cancers (Colombel et al, 1993;Joensuu et al, 1994) and it has been reported that bcl-2 expression is of prognostic significance in a number of malignancies (Baretton et al, 1996;Nakanishi et al, 1997;Nakopoulou et al, 1998), as is the expression of p53. In some cancers, bcl-2 expression correlates with negative p53 staining (which implies the presence of wildtype p53) (Silvestrini et al, 1994;Alderson et al, 1995;Fontanini et al, 1995).…”

Poorly differentiated synovial sarcoma: A case report

“…By contrast, when p53 is mutated, its half-life becomes longer, it accumulates at nuclear level and DNA-damaged cells can continue to proliferate, resulting in tumor. Recently, Nakanishi 17 found that 27% of synovial sarcoma were p53 positive and he consiclered this data indicative of abnormal accumulation of p53. P53 presence in this tumor could be expression of nuclear damage, but this fact alone is not helpful in pathogenetic speculation.…”

“…Analogously, Nicholson 18 and Suster 25 found Bcl-2 positivity in 100% of synovial sarcomas. Segers 23 and Nakanishi 17 found that synovial sarcoma could be also Bcl-2 negative. In addition, Nakanishi 17 underlined the possibility that patients with Bcl-2 positive soft tissue tumors showed more favourable prognosis than those Bcl-2 negative.…”

“…Segers 23 and Nakanishi 17 found that synovial sarcoma could be also Bcl-2 negative. In addition, Nakanishi 17 underlined the possibility that patients with Bcl-2 positive soft tissue tumors showed more favourable prognosis than those Bcl-2 negative. He suggested that the immunohistochemical detection of Bcl-2 could be useful to predict the prognosis of patients with soft tissue tumors, as confirmed by other studies.…”