Histopathological Evaluation of Apoptosis in Cancer

Soini, Ylermi; Pääkkö, Paavo; Vp, Lehto

doi:10.1016/s0002-9440(10)65649-0

Cited by 209 publications

(174 citation statements)

References 145 publications

(194 reference statements)

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“…However, the prognostic value of the frequency of apoptotic tumor cells is still controversial (25). In the present study, the extent of apoptosis (TUNEL-I) in primary synovial sarcomas showed a significant linear correlation with the mitotic rate (MI) and cell proliferative activity determined by Ki-67 immunostaining (MIB1-I).…”

Section: Discussionmentioning

confidence: 51%

“…Apoptosis in human cancers has been described in relation to high tumor grade, progression, and high mitotic rate (25)(26)(27)(28). However, the prognostic value of the frequency of apoptotic tumor cells is still controversial (25).…”

Section: Discussionmentioning

confidence: 99%

“…Similar relationships between apoptosis and cell proliferation have been reported in other tumor types (26,29,30), suggesting a mechanistic link between apoptosis and cell proliferation. The rela- tionship between apoptosis and cell proliferation may be explained in part by the fact that many proteins operating in the cell cycle checkpoints (e.g., p53; Rb; cyclins D1, A, and B) are also regulators and inducers of apoptosis (25).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Significance of Apoptosis in Synovial Sarcoma: Correlation with Clinicopathologic Parameters, Cell Proliferative Activity, and Expression of Apoptosis-Related Proteins

et al. 2000

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bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ ‫؍‬ 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ ‫؍‬ 0.52, P ‫؍‬ 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prognostic Significance of Apoptosis in Synovial Sarcoma: Correlation with Clinicopathologic Parameters, Cell Proliferative Activity, and Expression of Apoptosis-Related Proteins

et al. 2000

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“…12 The balance of pro-and antiapoptosis Bcl-2 family members is critical in determining if a cell undergoes apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Altered or enhanced cellular proliferation is seen in various tumors and is influenced by a myriad of factors. Apoptosis requires a complex coordinated pathway involving various cell signaling and proteins through a cascade of events leading to cell death.…”

mentioning

confidence: 99%

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

et al. 2004

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Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2-12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2-15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2-80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (Po0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity Â percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (Po0.05). Finally, a Bcl-x : Bax ratio Z1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio Z1 (Po0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.

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Apoptosis, proliferation, and Fas (APO-1, CD95)/Fas ligand expression in medullary carcinoma of the breast

Yakirevich

Maroun²,

Cohen³

et al. 2000

J. Pathol.

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Medullary carcinoma (MC) of the breast is a unique subtype of infiltrating ductal carcinoma that is characterized by a prominent lymphoid infiltrate and improved prognosis. Activated granzyme B(+)/CD8(+) cytotoxic T-lymphocytes (CTLs) infiltrating tumour cell nests constitute a major subset within the lymphoid infiltrate. As CTLs destroy target tumour cells by triggering apoptosis, it would be of interest to determine whether the apoptotic rate in MC is increased. This study evaluates the extent of apoptosis in relation to Fas (APO-1, CD95)/Fas ligand (FasL) expression in MC. Fourteen cases of typical MC (TMC) and 15 cases of atypical MC (AMC) classified according to the Ridolfi criteria, as well as 19 cases of poorly differentiated infiltrating ductal carcinoma (PDC) were evaluated. The apoptotic index (AI) was assessed by the TUNEL method on paraffin-embedded tissue. Cell proliferation was evaluated immunohistochemically by PCNA staining. The level of Fas/FasL expression was determined semiquantitatively by immunohistochemistry using a four-grade scoring system. The AI was significantly increased in TMC and AMC as opposed to the PDC subgroup (2.2+/-0.8, 2.1+/-0.8, and 1.3+/-0.6, respectively; p<0.05). A significant proportion (31.8+/-7.9% in TMC and 25.8+/-9.7% in AMC) of the apoptotic tumour cells within tumour nests were in close contact with CD3(+) lymphocytes. Increased apoptosis was not accompanied by increased proliferation of tumour cells. The extent of Fas expression did not differ between the three subgroups. FasL was expressed both by tumour infiltrating lymphocytes in MC and by tumour epithelium in all three subgroups. The observation that the majority of MCs express Fas and are infiltrated by lymphocytes expressing FasL suggests that increased apoptosis in MC is mediated by Fas/FasL. However, our observation that the majority of MCs also express FasL and the fact that tumours co-expressing Fas and FasL did not show increased apoptosis suggest that there may be additional cytotoxic pathways that lead to tumour apoptosis in MC.

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Histopathological Evaluation of Apoptosis in Cancer

Cited by 209 publications

References 145 publications

Prognostic Significance of Apoptosis in Synovial Sarcoma: Correlation with Clinicopathologic Parameters, Cell Proliferative Activity, and Expression of Apoptosis-Related Proteins

Prognostic Significance of Apoptosis in Synovial Sarcoma: Correlation with Clinicopathologic Parameters, Cell Proliferative Activity, and Expression of Apoptosis-Related Proteins

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

Apoptosis, proliferation, and Fas (APO-1, CD95)/Fas ligand expression in medullary carcinoma of the breast

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