Colorectal mesenchymal tumors - from smooth muscle tumors to stromal tumors

Colorectal mesenchymal tumors are rare. Therefore, distinguishing between gastrointestinal stromal (GIST) and smooth muscle tumors is important. This study aimed to delineate the immunophenotype and prognostic factors of 75 colorectal mesenchymal tumors. Fifty-three GIST and 22 smooth muscle tumor specimens were included from 1986 to 2007. Forty of 53 GIST were initially diagnosed as smooth muscle tumors and re-diagnosed as CD117 (+) GIST. Immunohistochemical studies were performed with antibodies of CD117, CD34, smooth muscle actin (SMA), desmin, S-100, Ki-67 and PCNA for clinicopathologic and prognostic correlation. In comparison, colorectal GIST exhibited a larger tumor size (P<0.001), higher mitotic count (P<0.001), higher cellularity (P<0.001), less spindle cell type (P=0.004), higher nuclear pleomorphism (P=0.004), and a higher NIH risk (P<0.001) than that of smooth muscle tumors. Positive immunoreactivities of GIST to a panel of antibodies were 88.6% to CD34, 28.3% to SMA, 1.8% to S-100 and 15.1% to desmin. For 75 mesenchymal tumors, survival analyses revealed that older patients (P=0.006), with a large tumor size (P<0.001), high mitotic count (P<0.001), increased NIH risk (P<0.001), non-spindle cell type (P<0.001), high cellularity (P=0.015), high cell pleomorphism (P<0.001), positive Ki-67 (P<0.001), high PCNA (P<0.001) and GIST (P=0.001) had a shorter disease-free survival than that of comparative groups. When the analyses concentrated on 53 GIST, the cell type and cellularity were no longer viable prognostic factors. The tumor mitotic count was the only independent prognostic factor for either mesenchymal tumors or GIST. In conclusion, GIST exhibited heterogeneous characteristics and was significantly larger, more mitotic and a poorer prognostic factor than smooth muscle tumor. The mitotic count is still the most valuable prognostic factor for colorectal mesenchymal tumors after KIT.     

胃肠道间质瘤40例Ki-67、PCNA的表达及意义

目的：探讨Ki-67、PCNA的表达与胃肠道间质瘤（GIST）临床病理特征的关系。方法：应用免疫组化SP法检测40例胃肠道间质瘤中Ki-67、PCNA的表达。结果：40例胃肠道间质瘤中Ki-67、PCNA阳性表达率分别为60．0％、65．0％。Ki-67、PCNA表达与GIsT的性别、年龄、部位、组织学分型无关,与肿瘤大小、组织学分级有关。Ki-67、PCNA的表达呈正相关。结论：Ki-67、PCNA联合检测可作为判定GIST良恶性、恶性程度、肿瘤分级及预后的重要指标。     

胃肠道间质瘤预后多因素分析

目的探讨胃肠道间质瘤的相关预后因素。方法复阅切片,重新诊断,从肿瘤的两点取材,构建组织微阵列。以免疫组织化学染色检测CD117、CD34、SMA、Desmin及S-100 5种蛋白的表达,分析各临床病理变量与预后的关系。结果194例患者1,3,5年生存率分别为93．5％、72．1％和63．2％;单因素分析显示,患者的预后与肿瘤大小、核分裂相数目、肿瘤坏死、肿瘤部位、肿瘤细胞密集程度、肿瘤细胞类型、核异型性、出血、手术方式、周围脏器组织有无侵犯、黏膜有无受侵、性别等因素有关（P〈0．05）;多因素分析显示,周围组织肿瘤侵犯、肿瘤坏死、肿瘤大小、核分裂相数目及性别是影响预后的重要因素。结论肿瘤大小及核分裂相数目是影响预后的重要因素,但准确判别预后尚应结合肿瘤坏死、性别、肿瘤部位及其他病理参数进行。     

Ki-67在CD117阳性的中、高危险度胃肠道间质瘤中的表达及其意义

 目的　探讨Ki-67在CD117阳性的中、高危险度胃肠道间质瘤（GIST）中的表达及其临床意义。方法　检测Ki-67在CD117阳性的中危险度（GIST）18例、高危险度GIST 25例中的表达,与随访结果对照,并与极低危险度和低危险度组33例比较,分析Ki-67指数（LI）与危险度的关系。结果　中、高危险度组随访40例,其中26例健在,高危组7例、中危组5例死于GIST,另2例死于其他原因。Ki-67 LI> 5 %在危险度中、高组与极低和低组间表达差异有统计学意义（P＜0.01）,Ki-67 LI还与核分裂象计数（MI）（＞5／50 HPF）、肿瘤大小（＞5 cm）相关（P＜0.05）,与部位无关（P＞0.05）。结论　Ki-67 LI＞5 %与肿瘤大小＞5 cm、MI＞5／50 HPF一起可作为CD117阳性的GIST中、高危险度的有用评价指标。     

Serosal penetration is an important prognostic factor for gastrointestinal stromal tumors

Predicting the malignant potential of gastrointestinal stromal tumors (GISTs) remains difficult. We assessed the value of serosal penetration, an established prognostic factor in solid tumors, to determine the clinical outcome in patients with GISTs. From 1996-2002, 25 consecutive patients with GIST underwent surgical resection at our Department. The histopathological presence of serosal penetration was assessed to predict clinical outcome. In addition, the established histopathological classification system by Franquemont (modified by using the Ki-67 proliferation index), was applied to each study patient. A Ki-67 index > or =5% (p<0.001) and a mitotic rate > or =5/50 high-power fields (p<0.047) significantly correlated with a shorter survival, whereas a tumor size >5 cm (p=0.07) tended towards a worse prognosis. The survival of patient groups defined by Franquemont (p=0.03) were of prognostic relevance. The presence of serosal penetration significantly correlated (p<0.01) with a shorter survival. Our data suggest that the presence of serosal penetration is a negative prognostic factor for GISTs. Serosal penetration may become a useful additional parameter for the classification of the malignant potential of GISTs. Since our data are merely hypothesis-generating, serosal penetration should be evaluated in large prospective databases.     

胃肠道间质瘤免疫表型的表达及临床意义

目的:观察胃肠道间质瘤（GIST）免疫表型的表达,分析其在诊断上的临床意义,探讨其与危险度分级的关系。方法:吉林大学第一医院病理科2010 年 12 月至 2012 年 8月检测的GIST术后标本65 例,采用免疫组化SP法检测CD117、CD34、DOG1、SMA、S-100、Ki-67和Desmin的表达,应用SPSS 17.0对数据进行分析,探讨相关免疫表型与临床病理相关因素的关系。结果:65例GIST中DOG1、CD117、CD34 的阳性率分别为100.0%、96.9%、89.2%。CD34在胃GIST的阳性表达高于小肠GIST(P＜0.05),SMA在小肠GIST的阳性表达高于胃GIST(P＜0.05),Ki-67的表达与肿瘤大小、核分裂相、危险度分级相关。结论:CD117联合CD34、DOG1检测可以提高GIST的诊断率;SMA在小肠GIST中表达率明显高于胃GIST的表达,CD34在胃GIST中表达率高于小肠GIST的表达;Ki-67可以作为一个判定GIST预后的指标。     

胃肠道及胃肠道外间质瘤的临床病理及免疫组化分析

目的:研究胃肠道及胃肠道外间质瘤的临床病理及免疫组化特点。方法:应用光学显微镜观察20例胃肠道及胃肠道外间质瘤的形态特征,用免疫组化SP法检测CD117、CD34、Vimentin、SMA、desmin及S-100等6种抗体的表达情况。结果:20例间质瘤中,女性11例,男性9例,平均年龄59·82岁(27~80岁)。发生部位:胃8例(40%),小肠4例(20%),大肠2例(10%),食管1例(5%),肠系膜4例(20%),大网膜1例(5%)。肿瘤镜下主要由梭形和上皮样细胞组成,有栅栏状、交叉束状、漩涡状及巢状等多种排列。CD117、CD34、Vimentin、SMA、desmin及S-100表达阳性率分别为95%(19/20),75%(15/20),100%(20/20),40%(8/20),5%(1/20)及25%(5/20)。临床症状以腹部包块、腹部不适及消化道出血为主。良性3例(3/20),潜在恶性4例(4/20),恶性13例(13/20)。恶性间质瘤中的核分裂>5/50HPF、肿瘤细胞坏死及细胞密集比良性和低度恶性者常见(P<0·05)。结论:间质瘤多发生于老年人,无性别差异,胃肠道是其好发部位,细胞排列多样,具有多向分化能力,免疫组化证实部分GIST具有不完全的平滑肌、神经单向或双向分化特征。核分裂>5/50HPF、肿瘤细胞坏死及细胞密集是重要的恶性指征。CD117及CD34是其较特异及敏感的抗体,免疫组化在间质瘤的诊断及鉴别诊断中起重要作用。     

Prognostic assessment of gastrointestinal stromal tumor

The term "gastrointestinal stromal tumor" (GIST) has been applied to a collection of distinctive mesenchymal tumors occurring within the human gastrointestinal tract. As new drug therapy becomes available, data regarding the natural history of these unusual tumors are necessary to provide selection factors for treatment. Ninety-eight patients had light microscopy compatible with GIST at a single institution from 1989 to 2000. After immunostaining with c-kit and histopathologic review, 69 were judged to be GIST. All prognostic indicators were determined for gastric GIST, intestinal GIST, and all locations combined. The location of the GIST did not have a significant impact on survival. Clinically, tumor size, peritoneal cancer index, and completeness of cytoreduction had a significant impact on prognosis for GIST at all locations. Pathologically, cytologic atypia, necrosis, invasion and number of mitoses were significant prognostic indicators for GIST. Criteria to separate three pathologic groups of GIST according to the tumor size and the mitotic count were useful to evaluate the tumor behavior; in the borderline pathologic group invasion and cytologic atypia were statistically significant prognostic criteria. The cell phenotypes, as determined by immunostains, correlated with the prognosis of gastric GIST but not intestinal GIST. A correlation between the immunostain Ki-67 but not CD-34 or desmin and the prognosis was observed. It is possible to select clinical and pathologic parameters of GIST that impact on prognosis. Invasion and necrosis help to determine the prognosis with borderline tumors. The immunostain Ki-67 correlated with the prognosis and may be helpful to assess prognosis when dealing with small biopsy specimens.     

Immunoreactivity of p53, Ki-67, and c-erbB-2 in phyllodes tumors of the breast in correlation with clinical and morphologic features

BACKGROUND AND OBJECTIVES: Phyllodes tumor (PT) is a biphasic tumor with unpredictable behavior. Our study aimed to evaluate clinicopathologic factors and biomarkers that may be helpful in predicting the outcome of these tumors. METHODS: We evaluated immunoreactivity of p53, c-erbB-2, and Ki-67 in 23 PT treated over a 10-year period. The proliferative activity in PT and expression of p53 and c-erbB-2 were correlated with clinicopathologic features of the tumors and patients' outcome. RESULTS: Positive stromal p53 immunoreactivity was found in PT with atypia, infiltrative borders, high cellularity, as well as in PT that displayed higher then average proliferation index, although none of these parameters reached statistical significance. There was a good correlation between proliferative stromal cell activity expressed Ki-67-labeling index and the malignant features of the tumors. Primary tumors that recurred displayed high proliferative activity. Three of four recurrent tumors showed a progression toward higher malignant phenotype with concomitant increase in proliferative stromal cell activity. c-erbB-2-positive tumors had no particular histologic features or association with either p53 positivity or higher proliferative indices. CONCLUSIONS: p53 expression tends to be more frequent in PT with higher malignant potential but did not predict recurrence. Incompletely excised tumors that recurred displayed high proliferative activity in their primary tumors. Progression toward more malignant phenotype in the recurrent PT was accompanied with increase in stromal cell proliferative activity, suggesting the presence of biological continuity between benign, borderline, and malignant PT.     

Biological analysis of gastrointestinal stromal tumors

The biological behaviour of a gastrointestinal stromal tumor (GIST) cannot be easily predicted from preoperative clinical examination alone. As a result, there is little standardization in the surgical treatment of GIST. In this study, we analyzed the clinicopathology and immunohistochemistry of 20 cases of GIST to clarify factors associated with tumors showing malignant potential. Immunohistochemical analysis of KIT, CD34, vimentin, alpha-smooth muscle actin (SMA), s-100, p53, ki-67, bcl-2 and bax expression was performed on 20 surgically resected GIST. An apoptotic index (AI) was calculated for each sample using a TdT-mediated dUTP-biotin nick end-labeling method. With regard to bcl-2, t(14;18) translocations were also investigated using a polymerase chain reaction based method. Finally, the relationship between these biological results and clinicopathological data was analyzed. Of the 20 cases studied, two patients died due to lung or liver metastasis. All cases stained positive for vimentin, nine cases were positive for alpha-SMA and three cases positive for s-100. All cases were stained for both KIT and CD34, which tended to correlate with malignant potential. There was significant difference in frequency of bcl-2 overexpression (p<0.05) and trend in Ki-67 labeling index (p=0.098) between benign and malignant cases. However, with regard to bcl-2, no chromosomal t(14;18) translocations were detected in four analyzed cases. In GIST, overexpression of bcl-2 may play an important role in increasing malignant potential. Furthermore, Ki-67 L.I. and bcl-2 overexpression may be useful in predicting malignant potential, and therefore help to determine the surgical treatment, follow-up manner, and the necessity of adjuvant therapy.     

Expression of vascular endothelial growth factor and angiogenesis in gastrointestinal stromal tumor of the stomach

Vascular endothelial growth factor (VEGF) is associated with the malignant potential of several types of carcinoma. The aim of this study was to elucidate the clinical significance of VEGF expression in gastrointestinal stromal tumor (GIST). METHODS: Specimens obtained from 53 patients who had underwent surgical resection for GIST of the stomach were used in this study. Specimens were examined immunohistochemically for VEGF expression and Ki-67 expression. Tumor microvessel density (MVD) was determined immunohistochemically with anti-CD31 antibody, and was estimated by averaging the counts from three high-power fields in the area showing the greatest neovascularization. RESULTS: VEGF expression was detected in 14 (26.4%) of the 53 lesions and correlated significantly with tumor size, liver metastasis, Ki-67 labeling index, and MVD. Prognosis was significantly poorer than in patients with tumors expressing VEGF than in patients with tumors lacking VEGF expression. Multiple logistic regression analysis for 10-year survival showed VEGF expression and high mitotic rate to be independent predictor of a poor outcome. CONCLUSIONS: Angiogenesis associated with VEGF may play an important role in the progression of GIST. VEGF expression may serve as an indicator of a poor prognosis.     

Ki-67、VEGF在胃肠间质瘤中表达及与MVD的相关性

目的:探讨Ki-67和VEGF在胃肠间质瘤中的表达及与临床病理因素的关系,VEGF、微血管密度(MVD)和细胞增殖之间的相关性。方法:采用免疫组化S-P法检测44例胃肠间质瘤组织中Ki-67、VEGF表达及计数MVD值和Ki-67PI。结果:VEGF、Ki-67在GIST组织中阳性表达分别为77.3%、63.6%,VEGF、Ki-67表达在不同大小的肿块之间有统计学差异(P<0.01);MVD值和Ki-67PI在VEGF阳性和阴性组的比较有统计学差异(P<0.01);VEGF、MVD和Ki-67PI之间呈显著正相关(相关系数分别为0.26、0.44和0.84,P<0.01)。结论:VEGF促进GIST组织中的新生血管形成,为肿瘤组织提供了丰富的血液和营养,并使细胞增殖活性增强,促进肿瘤细胞的增殖、肿瘤的生长、发展和转移;Ki-67PI为GIST的预后判断提供了比较客观的依据。     

直肠间叶性肿瘤的光镜及免疫组化观察

 目的　探讨直肠间叶性梭形细胞肿瘤的诊断与鉴别诊断和预后指标。方法　在光镜观察的基础上 ,运用免疫组化方法检测 1 5例直肠间叶性梭形细胞肿瘤的 Vimentin、Actin、Desmin、S- 1 0 0蛋白和 CD34的表达。结果　病理学确诊良性 2例 ,恶性 1 3例 ,肿瘤平均直径 6.8cm,平均核分裂数 8个 /1 0 HPF,并随 、分级增高而增多 ;免疫组化染色证实为平滑肌肿瘤 1 1例 (良性2例 ,恶性 9例 ) ,GIST 4例 ;随访 1 3例恶性肿瘤中有 3例复发 ,6例死亡 ,均为 、 级 ,其平均核分裂数 1 2个 /1 0 HPF。结论　肿瘤大小、核分裂数为直肠平滑肌肿瘤和 GIST良恶性诊断的重要指标 ;免疫组化染色有助于两者的鉴别诊断 ;瘤细胞异型性、核分裂多少与其预后有关。     

影响胃肠间质瘤患者预后的相关临床病理因素分析

目的分析影响胃肠间质瘤(GIST)患者预后的相关临床病理因素,为GIST的临床治疗提供参考。方法选取2013年1月至2015年10月柳州市中医医院普通外科收治的300例GIST患者,所有患者均行手术治疗,且于术后行病理和免疫组化检测,对其临床病理资料进行回顾性分析及随访,采用Cox风险模型分析影响GIST患者术后3年生存情况的临床病理因素。结果GIST患者3年生存率有差异的指标包括肿瘤切除情况、切缘阳性情况、有无破裂、有无转移、核分裂数、Ki 67指数、NIH分级和术后甲磺酸伊马替尼服用与否及服用疗程(P<005);Cox风险模型结果显示,肿瘤切除不完整、切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki 67指数>5％、NIH分级高危险性、术后未进行靶向治疗皆为影响GIST患者预后的独立危险因素(P<005)。结论影响GIST患者预后的独立危险因素有切缘阳性、肿瘤破裂、肿瘤转移、核分裂数增多、Ki 67指数>5％、NIH分级高危险性、术后未进行靶向治疗,临床治疗应结合各临床病理因素综合考虑,以准确判断患者的预后。     

Recent advances in cell biology, diagnosis, and therapy of gastrointestinal stromal tumor (GIST)

The understanding of mesenchymal neoplasms of the gastrointestinal tract has evolved dramatically over the last two decades since gastrointestinal stromal tumor (GIST) was described as the most common stromal tumor arising anywhere from the esophagus to the ano-rectum. Although morphologically similar to other benign and malignant smooth muscle and neural stromal neoplasms, GIST constitutes a distinct group of rare gastrointestinal tract tumors that originate from the interstitial cells of Cajal, regulators of gut peristalsis that normally express CD117, which is the product of the c-KIT proto-oncogene that encodes a tyrosine kinase receptor that regulates cellular proliferation in GISTs. Virtually all GISTs occur from mutations of the c-KIT oncogene and exhibit consistent expression of c-KIT (CD117), which is considered the most specific criterion for a diagnosis of GIST. Gastrointestinal stromal tumors vary in their behavior and several features have to be considered to assess their malignant potential. The advent of sophisticated imaging techniques for the evaluation and sampling of stromal tumors of the gastrointestinal tract has resulted in improved detection of GISTs. The identification of a novel tumor-specific target in c-KIT resulted in the development of a tyrosine kinase-inhibitor (imatinib mesylate) that provides an encouraging option for treating GISTs. This article reviews recent advances in the understanding of the cell biology, diagnosis, and therapy of GISTS.     

胃肠道间质瘤28例临床病理分析

目的探讨胃肠道间质瘤(GIST)的临床病理特点,分析其生物学行为与形态学的关系。方法回顾性总结分析28例GIST患者的临床病理资料,并复习相关文献。结果本组28例GIST患者中,发生在胃13例,小肠8例,结肠3例,食管2例,肠系膜1例,腹腔1例;高度恶性GIST 20例,低度恶性GIST 8例。镜下肿瘤组织由梭形细胞及上皮样细胞以不同比例混合而成。高度恶性GIST上皮样细胞比较增多。免疫组化标记显示CD117均为阳性。高度恶性组Ki-67阳性指数30%,低度恶性组Ki-67阳性指数3%。S-100及Actin仅2例灶状阳性,其余均阴性。结论上皮样细胞型GIST可能侵袭性更强,转移率更高;免疫组化标记Ki-67可能会成为评价其转移潜能的一个重要指标。     

Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: sequential analyses

Metastatic gastrointestinal stromal tumors (GIST) have an extremely poor prognosis; however, their immunohistochemical and genetic features have not been assessed satisfactorily and the mechanisms responsible for their high malignant potential remain unclear. We examined the immunohistochemical differences between gastric GIST and metastatic lesions in the liver of four patients who had undergone a postgastrectomy hepatectomy for metachronous liver metastases. We also carried out genetic analysis of the tumors in three of the four cases. In all cases, the immunoreactivity profiles, including KIT (CD117), CD34, smooth muscle actin (SMA), desmin, S-100 and vimentin, were similar between the gastric and metastatic tumors, but the Ki67 labeling index in the metastatic GIST was higher than that of the primary GIST. Interestingly, in the case who had received neoadjuvant imatinib therapy before gastrectomy, its therapeutic effect was observed in most of the primary lesion, with the exception of a specific small area with high cellularity. Genetic analysis revealed no acquired mutations in the c-kit or PDGFRA genes in the metastatic lesions in any of the patients, but loss of heterozygosity (LOH) of the c-kit gene was observed mainly in the metastatic tumors in two of the three cases. Furthermore, in the case of neoadjuvant imatinib therapy, LOH of the c-kit gene was shown in the high cellularity area in the primary lesion and metastatic liver GIST. It is suggested that LOH of the c-kit gene is an important event that leads to imatinib resistance and metastatic progression of GIST. In conclusion, both gastric and metastatic GIST had almost the same immunohistochemical features, except for their proliferative activity, and LOH of the c-kit gene played an important role in the process of liver metastasis.     

Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population-based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990-2003 were evaluated with an immunohistochemical panel including staining for c-kit. The age-adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty-seven of the mesenchymal gastrointestinal tumors were positive for c-kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high-risk category while half of the nongastric tumors (11 of 22) fall into this high-risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high-risk category is 46%. The negative predictive value of low- and very-low-risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population-based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs.     

Immunohistochemical profile of phyllodes tumors of the breast

The immunohistochemical profiles of 16 cases of phyllodes tumor of the breast (9 benign and 7 malignant) from 15 patients were examined by the labeled streptavidin biotin method. The expression of Ki-67, p53, bcl-2, alpha-smooth muscle actin (alpha-SMA), desmin, S-100 protein, estrogen receptor (ER), and progesterone receptor (PgR) was analyzed. The number of Ki-67-positive stromal cell nuclei of malignant phyllodes tumor were significantly more prominent than the benign tumors. The p53 expression on the stromal cell nuclei showed a significant difference between malignant and benign cases (86% vs 22%; p<0.05). bcl-2 was regularly seen on the luminal cell cytoplasm and stromal cell labeling showed no significant difference between malignant and benign cases (29% vs 33%). Stromal cells were alpha-SMA positive but refractory among cases, and desmin and S-100 protein were negative. PgR was expressed in all 16 cases and ER in most cases (12/16) the expression of which was restricted to luminal epithelial cell nuclei. These findings indicate that the Ki-67 labeling index and p53 expression in the stroma would be a good diagnostic parameter distinguishing benign tumors from malignant tumors. However, the absence of steroid receptor expression in stromal cells suggests the ineffectiveness of hormonal therapy for phyllodes tumor of the breast.     

Imaging of soft-tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine single photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity.

The radiolabeled amino acid L-3-[123I]-iodo-alpha-methyltyrosine (IMT) is a new tumor tracer that accumulates in many tumors and is suitable for single photon emission computed tomography (SPECT) imaging. Using IMT SPECT, we studied 32 patients with a soft-tissue tumor suspected to be a soft-tissue sarcoma to determine whether: (a) tumors can be visualized; (b) benign and malignant lesions can be distinguished; and (c) IMT uptake is related to tumor grade and proliferation. Whole-body imaging was performed 15 min after administration of 300 MBq IMT, biopsy, or resection 1-2 weeks later. IMT uptake was quantified using a region-of-interest method resulting in tumor:background (T:B) ratios. These were compared with tumor grade, mitotic index, tumor cellularity, vascularity, and the Ki-67 proliferation index. Eleven patients had a benign tumor, and 21 patients had a soft-tissue sarcoma. Six benign tumors demonstrated minor IMT uptake, and five lipomas had no uptake. All malignant tumors had high uptake and were clearly visualized. T:B ratios in malignant tumors (3.83 +/- 1.16) were higher (P < 0.001) than in benign tumors (1.52 +/- 0.60). Small (<5 mm) metastases in two patients were not detected. Taking the T:B ratio 2.0 as the cutoff level, the sensitivity for detection of malignancy was 100%, and specificity was 88%. IMT uptake correlated with histological grade (r = 0.82; P < 0.001), mitotic index (r = 0.75; P < 0.001), tumor cellularity (r = 0.73; P < 0.01), and with the Ki-67 proliferation index (r = 0.63; P < 0.01). In conclusion, IMT SPECT visualized all soft-tissue sarcomas. Uptake in sarcomas was clearly higher than in benign lesions, yielding 100% sensitivity for detection of malignancy at 88% specificity. Uptake increased with higher tumor grade and higher proliferation rate.