Antiproliferative effect of octreotide in somatotroph pituitary adenomas: discussion from a single case report

Summary  The case of a 20-year-old man presenting with a rapidly expanding pituitary somatotrophic adenoma with a tumour volume doubling time of 426 days is reported. Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating cells were absent at the time of tumoural resection. The correlation between clinical and proliferation markers data in this single case report affords an opportunity to discuss the antitumoral effect of octreotide on somatotrophic adenomas which may result from a suppression of cell proliferation.     

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas

Summary In order to improve our ability to predict the regrowth of nonfunctioning pituitary adenomas, we tried to assess the correlation between growth fractions with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling times in regrowing tumours, and also to find out any difference of growth fractions between the regrowing and the cured cases.In 33 patients with non-functioning pituitary adenomas, 14 cases including 11 with cavernous sinus invasion showed residual tumour on MRI after the operation (regrowing group) and 19 cases had no tumour regrowth on MRI within 5 years after the operation (cured group). Immunocytochemical studies were done with monoclonal antibodies (anti-PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by calculating the ratio of the positive nuclei to the total number of tumour cells with the aid of an image analyser (Mac SCOPE). The tumour doubling times were estimated from serial CT or MRI with the aid of the image analyser (NIH image).Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86±0.10%; mean±SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23±0.03%) in the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to 24% (n = 14, 3.7±1.6%). In the regrowing group, the tumour doubling times ranged from 200 to 2550 days (930±180 days), and showed a significant inverse correlation with Ki-67 staining indices, but no correlation with PCNA staining indices. The regrowing group showed a significantly higher Ki-67 staining index (n = 14, 0.86±0.10%) than the cured group (n = 19, 0.23±0.03%) (p<0.01).These results indicate that immunocytochemical studies using MIB-1 may be better than those with PCNA for the prediction of regrowth in non-functioning pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the accurate prediction of the rapid regrowing lesions in non-functioning adenomas.     

The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases

Summary. Background. Meningiomas are mostly benign tumours that can be cured by surgical resection. Because meningiomas tend to recur, long term management in patients with subtotal tumour resection remains controversial. Previous studies have shown that the proliferation potential of meningiomas by Ki-67 labelling indices (LI) might predict their natural history. The purpose of this study was to analyse the reliability of Ki-67-labelling index in predicting the behaviour of meningiomas, and to help the neurosurgeon in establishing better follow up criteria and long term management strategies for these patients. Method. From 1990 to 2000 1328 meningiomas have been operated in our Neurosurgical Department. A total of 600 tumours were examined immunohistochemically using the Mib-1 monoclonal antibody. Clinical charts of the patients including surgical, histological and follow up records, as well as imaging studies were analysed retrospectively. Ki-67 LI were correlated with neuroradiological findings, 3D volumetric studies, histological subtype, recurrence-free survival, grade of resection, consistency of tumour tissue, location, osseous involvement, en plaque appearance, vascularity and progesterone-receptor status. Findings. Among the 600 patients analysed, there were 66% females (mean LI 3.8%) and 34% males (mean LI 5.7%), including 20 neurofibromatosis-type-2 (NF-II) patients with a mean LI of 5.2%. Histological grading revealed 91% WHO°I meningiomas (mean LI 3.28%), 7% WHO°II (mean LI 9.95%) and 2% WHO°III (mean LI 12.18%). Labelling indices in recurrent meningiomas increased from initial resection to a fourth local resection. A significant correlation between negative progesteron-receptor status and high tumour vascularity with high Ki-67 LI was seen. Ki67 was not a statistically significant predictor of survival time in totally excised WHO°I meningiomas. Interpretation. Mib-1 is one important tool in addition to routine histological evaluation, but a combination of clinical factors and particularly the extent of surgical resection, along with the biological features of the tumour, should influence the decision of the neurosurgeon to the patient follow up.     

Ki-67 (clone MIB-1) proliferation index in recurrent glial neoplasms: no prognostic significance

Background To determine if the Ki-67 (MIB-1 clone) proliferative index (PI) has prognostic potential in patients with recurrent astroglial neoplasms.

Methods We conducted a retrospective review of 27 patients whose initial and recurrent specimens were available. Histopathology was determined according to the World Health Organization classification. Proliferation index was calculated on formalin-fixed tissue using the Ki-67 (MIB-1 clone) antibody. Morphometric data were analyzed in conjunction with clinical data and Cox Proportionate Hazards Analysis, Spearman’s correlation co-efficient and Mann-Whitney Test.

Results Initial histopathology included 14 glioblastoma multiforme, 7 anaplastic astrocytoma, 3 oligoastrocytoma, and 3 astrocytoma. Recurrent specimens showed changes consistent with treatment. While univariate analysis shows initial histology correlated with survival (p < 0.036), PI did not correlate with survival after either initial (p = 0.86) or recurrent (p = 0.46) surgery for any tumor type. PI difference between specimens also did not correlate with survival (p = 0.91). Initial PI did not correlate with recurrent PI either (p = 0.43).

Conclusions Ki-67 PI does not confer additional prognostic information for patients with recurrent astroglial neoplasms. One possible explanation for this observation is that treatment may alter the PI independent of its effect on tumor growth.     

Ki-67抗原与乳腺癌的相关性研究

目的探讨Ki-67抗原在乳腺癌组织中的表达,并评价其表达与乳腺癌生物学行为及判断乳腺癌预后的关系。方法检索近年来有关Ki-67与乳腺癌的相关性研究的文献并做综述。结果Ki-67在乳腺癌组织中的表达水平显著高于癌旁组织及正常乳腺组织,且Ki-67表达阳性率与乳腺癌病理分级、临床分期呈正相关,而Ki-67表达与乳腺癌腋窝淋巴结转移的相关性研究结果不尽一致。结论Ki-67抗原是与细胞增殖周期相关的细胞核抗原,其表达随细胞周期的变化而变化,是检测细胞增殖活性较为可靠的标志物,其可能成为判断肿瘤恶性程度及评估预后的重要指标;Ki-67表达水平的检测在乳腺肿瘤的早期诊断、指导新辅助化疗、评估预后等方面有重要意义。     

Hvin和Ki-67蛋白在胆管癌组织中表达的意义

目的 探讨Livin和Ki-67蛋白在胆管癌组织中的表达及两者之间的关系和临床意义.方法 采用SP法检测2002年1月至2003年12月中国医科大学附属盛京医院手术切除的55例胆管癌组织和12例慢性胆管炎组织中Livin和Ki-67蛋白的表达,并分析这两种蛋白与胆管癌临床病理特征的关系.应用Spearman等级相关分析、χ2检验和t检验对结果进行分析.结果 Livin蛋白在胆管癌标本中的阳性表达率为71%(39/55),明显高于慢性胆管炎标本的0(0/12)(χ2=20.361,P<0.01);Livin蛋白的表达受胆管癌患者的分化程度和淋巴结转移影响(χ2=4.193,4.245,P<0.05).Ki-67蛋白在胆管癌标本中的阳性表达率为96%(53/55).临床Ⅰ、Ⅱ、Ⅲ、Ⅳ期患者Ki-67标记指数分别为22%±16%、33%±12%、43%±15%、49%±10%,Ⅱ、Ⅲ、Ⅳ期与Ⅰ期比较差异有统计学意义(t=2.307,2.871,3.957,P<0.05);有无局部淋巴结转移的患者Ki-67标记指数分别为43%±13%、34%±16%,两者比较差异有统计学意义(t=2.334,P<0.05).胆管癌组织中Livin蛋白的表达与Ki-67标记指数呈正相关(r=0.502,P<0.01).结论 Livin蛋白在胆管癌的发生、发展中起重要作用,并且与胆管癌增殖活性相关,两者结合可作为胆管癌恶性程度和判断预后的标准.     

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

Runx3和Ki-67蛋白在皮肤恶性黑色素瘤中的表达

目的：检测Runx3和Ki-67蛋白在皮肤恶性黑色素瘤（CMM）中的表达水平,以探讨Runx3和Ki-67在CMM发生、发展过程中的作用。方法：采用免疫组织化学法研究Runx3和Ki-67蛋白在皮肤恶性黑色素瘤、皮肤交界痣及正常皮肤中的表达。结果：Runx3蛋白在CMM中阳性表达率为23.68%,与皮肤交界痣（85.00%）和正常皮肤（90.00%）相比,差异具有统计学意义（P〈0.05）;Ki-67蛋白在CMM中阳性表达率为78.95%,与皮肤交界痣（25.00%）和正常皮肤（25.00%）相比差异具有统计学意义（P〈0.05）。结论：皮肤恶性黑色素瘤的产生可能与Runx3蛋白的表达降低及Ki-67蛋白的表达升高有关。     

Surgery on pituitary adenomas in patients in a subarctic region

Summary The present series consists of 18 consecutive patients with pituitary adenomas operated on between 1977 and 1979 using the transfrontal route. Ten adenomas were 10, 20 or 30 times the normal maximum size of the pituitary measured according to Di Chiro and Nelson's (2) index (Table 2). Tumours without obvious suprasellar growth were operated on using the trans—sphenoidal route and thus are not included in the present series.Large and giant pituitary adenomas are preferably removed by the transfrontal route and using microsurgical techniques. Really poor vision associated with very large tumours seem to improve but not to normal level. A blind eye stays blind. Less poor vision returns to normal (Table 4). Prolactin values associated with giant prolactinomas are extremely high and may remain raised even after apparently radical extirpation. Isolated tumour-containing sellar crypts associated with these large tumours may be responsible for this observation. Postoperative radiotherapy and bromocriptine administration therefore seem advisable. Further operations may be necessary on patients with extensive posterior or lateral growths. Redundant partially intraosseal tumour fragments may be more easily removed later, possibly owing to the beneficial effects of radiation therapy. It is hoped that large and giant adenomas in the future will pass into history, even in the peripheral parts of the world. The trans—sphenoidal approach is always a better solution than the transfrontal approach whenever it can be carried out, but it requires earlier diagnosis.Presented at the 32. Scandinavian Neurosurgical Society Meeting in Linköping, September 3–6, 1980.     

PCNA and Ki-67 as Prognostic Markers in Human Parathyroid Carcinomas

Background: It is widely accepted that histological diagnosis of parathyroid tumors is established with great difficulty. Carcinomas cannot be reliably separated from adenomas by histology alone. In this study, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and Ki-67 was determined in 10 cases of parathyroid carcinomas, labeling indices (LIs) were calculated, and the results were correlated with the clinical outcomes.Methods: Ten cases of formalin-fixed, paraffin-embedded tissue with surgically resected parathyroid carcinoma were used. Immunohistochemical staining for PCNA and Ki-67 was performed and the LIs were calculated. We also examined whether LI could become a useful marker for parathyroid carcinomas.Results: Although nine patients with minimally invasive growth without recurrence of the tumor showed a low LI for both markers, one patient with a widely invasive neoplasm, and who died, had a high LI.Conclusions: These results suggested that the LI of PCNA and Ki-67, in addition to the histological appearance, may be markers of the biological behavior of parathyroid carcinomas. However, this study was on a small scale, so it may be valuable to repeat these studies in a larger group of patients with better defined histological criteria.     

Prognostic value of cell proliferation (Ki-67 antigen) and nuclear DNA content in clinically resectable, distal bile duct carcinoma

Background: The aim of this study was to investigate the prognostic value of cell proliferation (Ki-67 antigen) and DNA content in patients resected for distal bile duct carcinoma (DBDC). Methods: Formalin-fixed tumor specimens of 35 patients with resected DBDC and a long-term clinical follow-up were analyzed. MIB-1 antibody was used for Ki-67 antigen detection to determine the proportion of proliferating cells. DNA content was measured using flow cytometry. Results: A significant correlation was found between a low MIB-1 index (<20%) and survival (P<.05). Of the 35 tumor specimens, 34 specimens were evaluable by flow cytometry: 22 carcinomas were diploid (65%), and 12 were aneuploid (35%). The median DNA index of aneuploid tumors was 1.36 (range, 1.09 to 1.76). No correlation of DNA-ploidy with survival time was found. Conclusion: In contrast to DNA-ploidy pattern, Ki-67 antigen expression showed prognostic significance in resectable DBDC. A Ki-67 positive ratio of 20% was associated with decreased survival time.     

Expression of cyclin kinase inhibitor p21/WAF1 protein in pituitary adenomas: correlations with endocrine activity,but not cell proliferation

Summary.  p21/WAF1 blocks cell cycle progression through inhibition of cyclin/cyclin-dependent kinases (cdks) complexes and, simultaneously, has been associated with cell cycle exit and the process of differentiation. In this series, the expression of p21/WAF1 was assessed immunohistochemically in 47 cases of pituitary adenomas in relation to endocrine activity and cell proliferation. To evaluate cell proliferation, a monoclonal antibody, MIB-1, against Ki-67 antigen was used in all of the available cases. The study revealed positive p21/WAF1 staining in 24 cases of 26 functioning parenchymas, whereas 14 cases of 21 non-functioning parenchymas stained negative. The MIB-1 index ranged from less than 1% to 5.1% (mean: less than 1.7%) in functioning adenomas, and from less than 1% to 3.6% (mean: less than 1.6%) in non-functioning adenomas. Regardless of endocrine activity, p21/WAF1 positivity did not correlate with the MIB-1 index. Double staining techniques revealed the co-expression of p21/WAF1/GH or p21/WAF1/PRL in functioning adenomas. In 22 cases of p21/WAF1-positive functioning adenomas, p21/WAF1 immunoreactivity was seen in the cytoplasma as well as nuclei. These results indicate that in pituitary adenomas, p21/WAF1 expression is associated with endocrine activity, but not with cell proliferation. Taken together with recent findings demonstrating that cytoplasmic p21/WAF1 acts as an inhibitor of apoptosis, it is possible that pituitary adenomas expressing cytoplasmic p21/WAF1 have resistance against DNA-damaging agents such as ionizing radiation.     

Developments in surgical treatment of pituitary adenomas

Summary Progress in pituitary surgery has arisen with the introduction of microsurgical technique, endocrinological functional tests and computerized tomography of the skull.Using such microsurgical procedures, the transsphenoidal approach to the sella with selective adenomectomy is rendered possible. Furthermore, this operative approach is recommended also for pituitary tumours growing symmetrically to the suprasellar region.Endocrinological functional tests permit exact measurement of pituitary insufficiency and hormonal excesses, including all hormones of the anterior pituitary; today, only 30% of the adenomas are regarded as hormonally inactive. The indication to operate, the approach and the extent of the operative procedures depend on these results. Further, the operative result can be controlled by endocrine tests; in this way treatment of acromegaly can be improved: in patients with intrasellar adenomas GH-excess can be normalized in 90% of the patients.Selective adenomectomy has also improved the treatment of Cushing's disease. In women with hyperprolactinemic amenorrhea, who wished to have children, ovarian cycles and pregnancy occurred. In the case of prolactinomas, for the first time medical treatment of pituitary adenomas has been successful. Computerized tomography of the skull is the most important examination in order to localize a tumour and to determine its extent whereby the operative procedure (transsphenoidal, transcranial) is decided. After operation, the radicality of the operation can thus be documented and in the case of tumour residuals a second operation may then be indicated.

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Zusammenfassung Die Fortschritte in der Hypophysenchirurgie basieren auf der mikrochirurgischen Technik, der endokrinologischen Funktionsdiagnostik sowie der Computer-Tomographie.Das mikrochirurgische Vorgehen hat den transsphenoidalen Zugang mit selektiver Adenomektomie ermöglicht. Darüber hinaus empfiehlt sich dieser Operationsweg auch bei symmetrisch suprasellär aus der Sella herausgewachsenen Geschwülsten.Endokrinologisch lassen sich mit Hilfe der Funktionsdiagnostik Hypophysen-Insuffizienzen und Hormon-Exzesse, die alle Vorderlappenhormone betreffen können, exakt bestimmen; als inaktiv gelten heute nur noch etwa 30% der Adenome. Von diesen Ergebnissen hängt die Indikation zur Operation, die Art und das Ausmaß des operativen Eingriffs ab. Darüber hinaus läßt sich der Operationserfolg endokrinologisch kontrollieren; auf diese Weise ist z. B. in der Behandlung der Akromegalie eine Normalisierung des GH-Exzesses bei 90% der intrasellären Adenome erreicht worden.Die selektive Adenomektomie hat auch die Behandlung des hypothalamisch/hypophysären Cushing-Syndroms bereichert und bei Frauen mit hyperprolaktinämischer Amenorrhoe und Kinderwunsch die Wiedererlangung ovarieller Zyklen und Schwangerschaften ermöglicht. Für die Prolaktinome zeichnet sich erstmals eine erfolgversprechende medikamentöse Therapie der Hypophysenadenome ab.Zur Lokalisation und Bestimmung der Ausdehnung der Geschwülste ist die Computer-Tomographie die entscheidende Untersuchung, welche die Wahl des operativen Zugangs (transsphenoidal, transkranial) bestimmt und postoperativ die Radikalität des Eingriffs belegt und im Falle verbliebener Tumorreste zu einer zweiten Operation, u. U. auf dem anderen Operationsweg, Anlaß geben kann.

     

Proliferation, Vascular Endothelial Growth Factor Expression and Cavernous Sinus Invasion in Growth Hormone Secreting Pituitary Adenomas

Summary  Surgical cure of growth hormone producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). Tumour proliferative activity and angiogenesis are thought to be required for tumour growth and invasion, and vascular endothelial growth factor (VEGF) activates neovascularization around tumours. In this study, the mechanism and clinical significance of CS invasion is analysed. In 25 surgically treated GHomas, the extent of CS invasion was classified as high (Knosp's grade 3 and 4), and low (grade 0, 1 and 2) MR grades, and the MR grades were compared with tumour proliferative potential (Ki-67 expression), angiogenetic demand (VEGF expression), volume of adenomas and serum hormone levels.  The Ki-67 index of high MR grade adenomas (1.17±0.62%) was significantly higher than that of low MR grade adenomas (0.55±0.42%, p=0.027), whereas VEGF expression showed no significant correlation with MR grades (p>0.999). Tumour volume also showed a significant correlation with MR grade (p=0.002). VEGF expression was not correlated with serum hormone level and volume, but was correlated with tumour proliferative potential. Proliferative potential and tumour volume were two independent factors related to CS invasion. Although VEGF expression was not a direct factor related to CS invasion, it may indirectly play a role in activation of tumour aggressiveness, which is required in CS invasion.  Our results show that high MR grade adenomas have higher proliferative ability. In order to improve the surgical outcome, pre-operative medical debulking is indicated, particularly, in such adenomas.     

膀胱移行细胞癌Ki-67的表达及其意义

目的:探讨Ki-67抗原在膀胱移行细胞癌(BTCC)中的定量表达及其与BTCC生物学行为的关系。方法:用流式细胞技术(FCM)对36例BTCC和10例正常膀胱黏膜细胞组织标本进行Ki-67检测。结果:Ki-67在BTCC组织中的阳性表达率为(10.89±7.88)%,在正常膀胱黏膜组织中的阳性表达率仅为(0.27±0.07)%,两者比较差异有统计学意义(P<0.01);临床分期Tis~T1为(4.93±2.95)%,T2~T4为(18.34±5.24)%,病理分级Ⅰ级为(3.17±0.83)%,Ⅱ级为(10.97±2.35)%,Ⅲ级为(21.60±3.70)%,随着分期分级的增加,Ki-67的表达率也逐步增加,差异有统计学意义(P<0.01)。结论:定量检测Ki-67能准确评估BTCC的生物学行为,Ki-67是膀胱癌的重要肿瘤标记物。     

自然流产小鼠蜕膜组织中PCNA、Ki-67和survivin表达水平的研究

目的比较正常妊娠和自然流产小鼠模型蜕膜组织中增殖细胞核抗原（PCNA）、细胞增殖标记物Ki-67和凋亡蛋白抑制因子suvivin的表达情况,探讨自然流产的发病机制。方法建立正常妊娠模型CBAXBALB／c和自然流产模型CBAXDBA／2。采用免疫组化SP法测定两组模型孕13d蜕膜细胞PCNA、Ki-67和suvivin的表达。结果与正常妊娠模型相比,自然流产模型蜕膜细胞PCNA的表达显著降低（P〈0．05）;Ki-67和survivin表达降低非常显著（P〈0．01）。结论自然流产小鼠蜕膜细胞PCNA、Ki-67和survivin表达水平低下可能与自然流产的发生有关。     

膀胱移行细胞癌中Survivin与Ki-67、p53的表达及临床意义

目的 探讨膀胱移行细胞癌中Survivin、p53及Ki-67的表达与膀胱移行细胞癌临床病理特征的关系及其临床意义. 方法 用免疫组织化学方法 检测88例膀胱移行细胞癌与10例正常膀胱黏膜组织中Survivin、p53及Ki-67的表达,并用RT-PCR方法 验证其中30例膀胱移行细胞癌和10例正常膀胱黏膜组织中Survivin的表达. 结果 免疫组织化学方法 显示在膀胱移行细胞癌中Survivin、p53阳性表达率分别为63.6%(56/88)和45.5%(40/88),正常膀胱黏膜组织中均无表达,差异有统计学意义(P<0.01),且Survivin的表达与膀胱癌的临床分期密切相关(P<0.05).膀胱癌组织中Ki-67增殖指数(PI)为20.4士10.7,正常膀胱黏膜组织中为0.RT-PCR方法 显示在30例膀胱移行细胞癌中Survivin阳性表达率为100%,而正常膀胱黏膜组织中均无表达.结论 Survivin与膀胱癌的恶性程度有关,与p53及Ki-67共同参与了膀胱移行细胞癌的发生、发展及进程.     

Ki-67抗原在血管瘤和血管畸形组织中的表达

目的探讨Ki-67抗原在血管瘤和血管畸形组织中的表达及其临床意义.方法应用免疫组织化学SP方法,测定各类血管瘤组织石蜡标本76例和正常皮肤11例中Ki-67抗原的表达.结果Ki-67抗原在增生期草莓状血管瘤中的表达阳性率为100%,与在消退期草莓状血管瘤、血管畸形和正常皮肤中的表达差异有统计学意义.结论测定Ki-67抗原的表达情况有助于区分血管瘤和血管畸形以及血管瘤的分期,对于进一步进行病因学的研究和正确的选择治疗方法具有重要意义.     

Clinical and cytofunctional classification of pituitary adenomas: Proposal of a new classification

Summary Recent methodological advances in immunohistochemistry, ultrastructural techniques, hormonal assays, resolution imaging and molecular biology techniques have provided new insights into the pathology, function and cytogenesis of pituitary adenomas. Pituitary adenomas have been classified historically on the basis of tinctorial affinities, followed by the basis of ultrastructure and immunohistochemistry. The current development of technologies necessitate the new classification of pituitary adenomas which integrates these numerous parameters as well as the clinical manifestations. For this purpose, we suggest a new clinico-cytofunctional classification of pituitary adenomas, which is based on these clinical manifestations and integrates the information on biology, imaging function and ultrastructure. This classification which corresponds to current advances will not only provide pertinent clinical data but facilitate better understanding of the biology and nature of these complexed lesions.     

Ki-67乳腺癌临床应用价值及其临界值界定的研究进展

Ki-67在临床上具有重要的应用价值,但其表达阳性率临界值的界定尚存有争议,给临床应用带来一定困难.本文总结了国内外在Ki-67对乳腺癌预后判断、临床指导治疗价值及其表 达阳性率临界值界定的研究,分析了各项研究存在差异的原因,并提出科学界定Ki-67表达阳性率临界值的必要性及临床重要性,从而为Ki-67在临床应用提供一定的理论依据.