Prognostic significance of the proportion of Ki-67-positive cells in adult t-cell leukemia

Yamada, Yasuaki; Murata, Ken T.; Atogami, Sunao; Tsukasaki, Kunihiro; Sohda, Hisashi; Yanagisako, T; Momita, Saburo; T, Jubashi; Amagasaki, T; Kuriyama, Kazutaka; Oyakawa, Yukinobu; Tagawa, Masuko; Ichimaru, Michito; Tomonaga, Masao; Kamihira, Shimeru; Kinoshita, K

doi:10.1002/1097-0142(19910515)67:10<2605::aid-cncr2820671034>3.0.co;2-l

Cited by 31 publications

(9 citation statements)

References 23 publications

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“…4 Several other prognostic factors have been identified, such as Ki 67 expression in the ATL cells, immunophenotypes other than the typical CD4 ϩ CD8 Ϫ ATL cells, defective HTLV-1 integration, and deletion of the p15INK4B or p16INK4A gene. [5][6][7][8] The incidence of ATL is relatively low among carriers of HTLV-1, and those in whom the disease develops usually have a 40-to 70-year latency period from the time of infection to progression to ATL. 9 A statistical analysis suggested that development of ATL requires 5 independent genetic events.…”

Section: Introductionmentioning

confidence: 59%

Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Tsukasaki

Krebs

Nagai

et al. 2001

Blood

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103

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Sixty-four patients with adult T-cell leukemia/lymphoma (ATL; 18 patients with indolent subtype and 46 with aggressive subtype) associated with human T-lymphotropic virus type 1 (HTLV-1) were analyzed using comparative genomic hybridization (CGH). The most frequent observations were gains at chromosomes 14q, 7q, and 3p and losses at chromosomes 6q and 13q. Chromosome imbalances, losses, and gains were more frequently observed in aggressive ATL than in indolent ATL, with significant differences between the 2 ATL subtypes at gains of 1q and 4q. An increased number of chromosomal imbalances was associated with a significantly shorter survival in all patients. A high number of chromosomal losses was associated with a poor prognosis in indolent ATL, whereas the presence of 7q؉ was marginally associated with a good prognosis in aggressive ATL. Paired samples (ie, samples obtained at different sites from 4 patients) and sequential samples from 13 patients (from 6 during both chronic disease and acute crisis and from 7 during both acute onset and relapse) were examined by CGH and Southern blotting for HTLV-1. All but 2 paired samples showed differences on CGH assessment. Two chronic/crisis samples showed distinct results regarding both CGH and HTLV-1 integration sites, indicating clonal changes in ATL at crisis. In 11 patients, the finding of identical HTLV-1 sites and clonally related CGH results suggested a common origin of sequential samples. In contrast to chronic/ crisis samples, CGH results with all acute/ relapse sample pairs showed the presence of clonally related but not evolutional subclones at relapse, thereby suggesting marked chromosomal instability. In summary, clonal diversity is common during progression of ATL, and CGH alterations are associated with clinical course. (Blood. 2001;97:3875-3881)

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Section: Introductionmentioning

confidence: 59%

Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Tsukasaki

Krebs

Nagai

et al. 2001

Blood

Self Cite

103

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“…It can be detected in formalinfixed tissue sections using immunohistochemical techniques. Its level of expression has prognostic value in several types of malignancies, including breast cancer, non-Hodgkin lymphomas and acute leukemias (14)(15)(16)(17). In primary malignant melanoma of the skin the proliferative activity has also been studied by several methods.…”

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confidence: 99%

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin

1996

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Nuclear morphometry, immunohistochemical staining with Ki-67 antibody and mitotic index were studied in primary cutaneous malignant melanomas. The number of Ki-67 positive cells/ 200 tumor cells did not correlate with any nuclear morphometrical parameters, and it only approached but did not reach significant correlation with melanoma thickness according to Breslow. The nuclear area, short axis and long axis correlated with melanoma thickness, but the nuclear axis ratio (which reflects the sphericity of nuclei) and melanoma thickness did not show significant correlation. Mitotic index was higher in thick melanomas and in melanomas with high Ki-67 positivity, large nuclear area, long nuclear short axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model, melanoma thickness and the nuclear axis ratio were significant independent prognostic factors for patient survival, while the nuclear area, short axis and long axis, gender, age, Clark level, mitotic index and Ki-67 positivity lacked significant independent prognostic value. The results suggest that the proliferative activity of tumor cells does not alone explain the great importance of tumor thickness as prognosticator in melanoma. The thickness of melanoma measured according to Breslow and the nuclear axis ratio are more efficient prognosticators in melanoma than parameters associated with proliferation.

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“…The serum lactate dehydrogenase (LDH) level shows a less significant inverse correlation with survival. 12 We suggest that a high level of Ki-67 positivity of cutaneous infiltrative cells, as in this case, may be a significant finding which, together with a high serum LDH level, reflects a poor prognosis of disease.…”

Section: Discussionmentioning

confidence: 51%

CD4/CD8 double-positive, acute type of adult T-cell leukemia/lymphoma with extensive cutaneous involvement

Kim¹,

Hwang²,

Kim³

et al. 2005

Int J Dermatol

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A 67-year-old Korean man presented with a 2-week history of pruritic cutaneous lesions on the trunk and a 2-month history of cervical neck masses. The cutaneous lesions had been spreading rapidly for the last week. The past history included an unknown liver disease about 40 years previously, and he had never been transfused. The physical examination revealed multiple cervical lymph node enlargements and a two-finger width of splenomegaly with tenderness. Numerous nodules and plaques were distributed on the trunk, face, and proximal extremities (Fig. 1). The results of laboratory tests were as follows: leukocyte count, 24,200/ mm 3 , with lymphocytes 15,560/mm 3 ; serum lactate dehydrogenase, 943 IU / L (normal range, 263 -450 IU/L); alkaline phosphatase, 135 IU/L (normal range, 35 -60 IU/ L); blood urea nitrogen, 32 mg /dL (normal range, 3 -24 mg/dL); serum creatinine, 1.7 mg / dL (normal range, 0.3 -1.6 mg/dL); serum calcium, 17.5 mg/dL (normal range, 8.8 -10.2 mg/dL). Other laboratory results, including liver function test and urine analysis, showed no abnormalities. The examination of peripheral blood revealed multilobulated atypical lymphoid cells. The radiologic images showed hilar, para-aortic lymph node enlargement and splenomegaly. A skin biopsy from the nodular lesion revealed massive infiltration of small-to medium-sized atypical lymphoid cells in the dermis (Fig. 2a). The infiltrating cells were positive for CD3 ( Fig. 2b), CD4 (Fig. 2c), CD5, and CD8 (Fig. 2d), but negative for CD20, CD34, CD56, CD68, and terminal deoxynucleotidyl transferase (TdT) in the immunohistochemical studies on paraffin sections.They also showed high Ki-67 labeling (80 -90%), and this finding reflects their highly proliferative nature. Polymerase chain reaction (PCR) analysis showed a distinct band for the T-cell γ receptor gene, confirming the T-cell clonality of the infiltrating neoplastic cells. Specimens from the cervical lymph node and bone marrow showed the same results in immunohistochemical studies. PCR analysis of the DNA from peripheral leukemic cells showed human T-cell leukemia virus type I (HTLV-I) proviral integration. The patient was diagnosed as having the acute type of adult T-cell leukemia / lymphoma (ATLL). The disease course was extremely aggressive, and he died of acute renal failure on the 16th day following diagnosis.

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Prognostic significance of the proportion of Ki-67-positive cells in adult t-cell leukemia

Cited by 31 publications

References 23 publications

Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course

Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin

CD4/CD8 double-positive, acute type of adult T-cell leukemia/lymphoma with extensive cutaneous involvement

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