流式细胞术和银染核仁区在乳癌诊治中的应用

作者对４３例乳腺肿物进行ＤＮＡ流式细胞术和ＡｇＮＯＲ检测。大多数ＤＮＡ异倍体为恶性病变（２３／２４），良性病变的ＳＰＦ和ＰＩ与二倍体癌相近，但低于异倍体癌（Ｐ＞０．０５）；二倍体癌ＳＰＦ和ＰＩ低于异倍体癌（Ｐ＜０．００１）。异倍体多见于腋淋巴结转移和年轻患者（Ｐ＜０．０５）。半数左右乳腺癌的ｍＡｇＮＯＲ高于良性病变的最高值。本研究表明ＤＮＡＦＣＭ和ＡｇＮＯＲ检测可作为良恶性病变鉴别的参考，异倍体癌临床进程较快，ＤＮＡ异倍体和高Ｓ１／Ｓ２，ｍＡｇＮＯＲ肿瘤有较强的浸润性，但对化疗也较敏感，应考虑行辅助化疗。     

乳腺癌原发灶及腋淋巴结的FCM检测

乳腺癌原发灶及腋淋巴结的ＦＣＭ检测宋心龙，赵祥生，朱继荣，周振英，张彤近年来，乳腺癌进行ＦＣＭ检测的报道不少。但对ＤＮＡ含量所反映的生物学特性尚未彻底认识，ＤＮＡ倍体与临床诸因素之间的关系亦有争论，腋淋巴结ＦＣＭ分析及其与原发灶倍体的关系尚未见报道。...     

胰腺肿瘤DNA含量检测及生存分析

作者对本院１９７９～１９９１年手术和病理证实的３２例胰腺癌、１０例邻近癌的胰腺组织、８例胰腺炎以及１６例胰岛细胞瘤石蜡包埋组织，用流式细胞仪（ＦＣＭ）检测其细胞核ＤＮＡ含量。结果发现：胰腺癌的异倍体率及ＤＮＡ指数明显高于胰腺非肿瘤病变者（Ｐ＜０．０１）；ＤＮＡ异倍体胰腺癌的Ｓ期比例亦明显高于二倍体胰腺癌（Ｐ＜０．０５）；胰腺癌细胞核ＤＮＡ含量的变化是一个相对独立的反映胰腺癌生物学行为的指标。ＤＮＡ二倍体胰腺癌患者的手术可切除率明显高于异倍体肿瘤患者（Ｐ＜０．０５）。采用Ｋａｐｌａｎ－Ｍｅｉｅｒ生存分析法显示，ＤＮＡ异倍体胰腺癌较二倍体者生存时间短，预后差（Ｐ＜０．０５％）。     

图像分析与流式细胞计在膀胱癌预后判断方面的比较

应用图像分析（ＩＣＭ）与流式细胞仪（ＦＣＭ）检测膀胱癌石蜡包埋标本的ＤＮＡ含量，在４５例标本中，ＩＣＭ检测出异倍体癌３１例，而ＦＣＭ检测出２０例。结果表明，在发现异倍体方面，ＩＣＭ比ＦＣＭ更为灵敏（Ｐ＜０．０２５）。简要地比较了两种定量分析方法的优缺点。     

乳腺癌骨髓微转移灶的检测及其临床意义

近年,有关乳腺癌为全身性疾病已达共识,即使是Ⅰ期病例,也有近１／１０会发生转移。以往根据病理类型、原发灶大小、腋淋巴结转移情况及雌激素受体测定等来筛选易复发或转移的高危病例。随着对肿瘤生物学特性的研究不断深入,发现很多因素可帮助判断乳腺癌病人的预后,诸如肿瘤Ｓ期细胞比例、是否异倍体肿瘤以及癌基因和抑癌基因表达等。此外,肿瘤的微转移也是一个重要因素。所谓微转移是指采用常规病理方法难以检出的实体瘤转移,可采用免疫组化、放射免疫法、流式细胞仪和ＲＴ－ＰＣＲ检测。对乳腺癌而言,主要有骨髓和腋淋巴结的微转…     

诺维本加阿霉素在局部晚期乳腺癌新辅助化疗中的应用

目的：了解诺维本加阿霉素的新辅助化疗方案在局部晚期乳腺癌综合治疗中的作用。方法：３１例Ⅱｂ至Ⅲｂ期的乳腺癌病人,术前均经病理或细胞学检查证实。中位年龄４８岁,化疗用药为ＮＶＢ ４０ｍｇ ｄ１,８＋ＡＤＭ ４０ｍｇ ｄｌ,每３周为一疗程,术前用药２疗程,评估新辅助化疗后肿瘤的缓解情况和随访长期生存率。结果：本组总体化疗有效率为６７．７％,肿瘤原发灶完全缓解（ＣＲ）１例,部分缓解（ＰＲ）２０例,无变化（ＳＤ）１０例;腋淋巴结临床ＣＲ１２例,ＰＲ１４例,ＳＤ５例。术后中位随访期３６个月,术后死亡６例,复发９例,健在１６例。结论：诺维本加阿霉素的联合术前化疗能使局部晚期乳腺癌的原发灶和腋淋巴结缩小,肿瘤降期,亦能减少肿瘤复发和远处转移,且不良反应较轻。     

乳腺癌血管生成与淋巴结转移的关系

为探讨乳腺癌血管生成与淋巴结转移的关系,作者采用免疫组织化学方法检测了１９８４年至１９８５年手术切除的７０例原发性乳腺癌石蜡标本组织中的微血管密度（ＭＶＤ）及血管内皮生长因子（ＶＥＧＦ）表达,其中有腋淋巴结转移（ＬＮ＋）者３１例,无腋淋巴结转移（ＬＮ－）者３９例。光镜下,２００倍视野计数ＭＶＤ,４００倍视野计数ＶＥＧＦ阳性细胞。结果显示：ＬＮ＋组的ＭＶＤ及ＶＥＧＦ表达显著高于ＬＮ－组;ＭＶＤ及ＶＥ     

小肠癌DNA倍体定量分析及其临床意义的研究

作者应用计算机图像分析ＤＮＡ定量的方法对２８例小肠癌、５例小肠腺瘤、６例正常小肠组织中的异倍体所占的比例及ＤＮＡ含量的１２个参数进行了检测。结果表明：小肠癌中的异倍体数量明显高于小肠腺瘤，其中ＤＮＡ熵值（ＥＤ）、２倍体偏移指数（２ＣＤＩ）、ＤＮＡ恶性分级（ＤＧＮ）、５倍体超过率（５ＣＥＲ）、９倍体超过率（９ＣＥＲ）、２倍体偏移熵数（ＤＤＱ）、平均倍体（ＭＰ）七个ＤＮＡ参数对判断小肠良、恶性病变有重要意义；ＤＮＡ含量与小肠癌的临床病理组织分化程度无关，但异倍体小肠癌较非异倍体小肠癌恶性度高，易发生浸润和转移，术后生存率低，预后较差。ＤＮＡ参数中的ＤＮＡ指数（ＤＩ）、众数值（ＭＶ）、ＤＮＡ恶性分级（ＤＧＮ）、干系倍体值（ＳＰ）、９倍体超过率（９ＣＥＲ）五个参数与小肠癌的预后关系密切，对分析小肠癌的预后有重要价值     

甲状腺乳头状癌复发与DNA倍体水平及C—erbB2表达——Cox模型多因素预后分析

收集病理存档的６９例甲状腺乳头状癌（ＰＴＣ）的石蜡包埋组织块，用流式细胞仪（ＦＣＭ）检测肿瘤细胞ＤＮＡ含量及免疫组织化学方法检测肿瘤细胞中癌基因Ｃ－ｅｒｂＢ２表达，同时结合临床随访资料包括性别、年龄、手术方式、肿瘤大小、颈部淋巴结情况，有无远处转移、病理分级、有无术后复发或死亡、复发或死亡的时间及原因等，应用Ｃｏｘ风险模型对上述资料进行多因素预后分析，发现影响ＰＴＣ术后复发的预后因素依次为ＤＮＡ倍     

原发性肝癌DNA含量与核形态学参数关系的分析及其临床意义

本研究图像分析技术（ＩＡＴ）对５５例原发性肝癌（ＰＨＣ）病人的ＤＮＡ含量及核形态学参数进行检测，结果显示：无１例ＰＨＣ的ＤＮＡ干系水平睡于ＤＮＡ含量二倍体区域，３例处于近二倍体（５．４５％），５２例处于异倍体（９４．５５％）。ＤＮＡ含量与有无淋巴结转移（Ｐ〈０．０５）、瘤体大小（Ｐ〈０．０１）、生存率（Ｐ〈０．００１）有相关性。核形态学参数与ＰＨＣ的ＤＮＡ含量及ＰＨＣ有无淋巴结转移亦有统计学意义。     

Relationship between DNA ploidy and survival in patients with primary breast cancer

The DNA ploidy of breast cancer tissue from paraffin blocks was measured by flow cytometry in 117 patients whose disease had been detected and treated with surgery between 1974 and 1976. Patients with aneuploid tumours had positive axillary nodes and distant metastases more often than those with diploid tumours. Aneuploid tumours were more common in postmenopausal than premenopausal women. The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumours and positive axillary lymph nodes were found in 26 per cent of the patients who had a tumour with a SPF below the median (4.8 per cent) and in 48 per cent of those with tumours with SPF values above the median. At the primary clinical investigation 2 per cent of the patients with diploid tumours and 6 per cent of those with aneuploid tumours had distant metastases. During the follow-up, the proportion of patients with distant metastases increased to 42 and 72 per cent, respectively. With a follow-up of 11.5 years, the DNA aneuploidy of the tumour showed a significant association with decreased survival. Thirty-three per cent of patients with diploid and 65 per cent of patients with aneuploid tumours had died from breast cancer during the follow-up (P less than 0.001). All patients with hypertetraploid or multiploid tumours died from breast cancer. High SPF values were associated more closely with distant metastases or death during the follow-up than low SPF values. Our results suggest that DNA ploidy measured by flow cytometry from paraffin embedded tissue blocks of human breast cancer can be used to predict the aggressiveness of the tumour and the survival of the patients.     

DNA ploidy level and S-phase fraction as prognostic factors in breast cancer

Imprint smears from sixty cases of breast cancer made after mastectomy were stained by the Feulgen method and the nuclear DNA content measured by a cytofluorometer equipped with an incident illumination system. After logarithmic transformation of the fluorescence intensity, the ploidy level and S-phase fraction (SPF) were calculated with a microcomputer and the correlation between the ploidy level or SPF and the clinicopathological prognostic factors studied. Patients with tumors of a larger diameter and more extensive lymph node involvement had higher levels of ploidy and SPF and the ploidy level in the metastatic lymph nodes was higher than that in the primary lesion. Moreover, a significant increase in SPF was observed in the metastatic lymph nodes and a high ploidy level found to be associated with tumors having a negative estrogen receptor. When the tumors were divided into a diploid group and an aneuploid group, the diploid group showed a significantly better prognosis than the aneuploid group, in 6-year survival. Similarly, the groups in which SPF was less than 20.0 per cent had significantly better prognoses than the group in which SPF was 20.1 per cent or more. These prognostic factors were evaluated with Cox's proportional hazard model and a significant correlation observed in lymph node status, ER status, ploidy level and S-phase fraction. It was thus concluded that ploidy level and SPF are important and independent prognostic factors for predicting the postoperative course of breast cancer patients.     

DNA ploidy level and S-phase fraction as prognostic factors in breast cancer

Imprint smears from sixty cases of breast cancer made after mastectomy were stained by the Feulgen method and the nuclear DNA content measured by a cytofluorometer equipped with an incident illumination system. After logarithmic transformation of the fluorescence intensity, the ploidy level and S-phase fraction (SPF) were calculated with a microcomputer and the correlation between the ploidy level or SPF and the clinicopathological prognostic factors studied. Patients with tumors of a larger diameter and more extensive lymph node involvement had higher levels of ploidy and SPF and the ploidy level in the metastatic lymph nodes was higher than that in the primary lesion. Moreover, a significant increase in SPF was observed in the metastatic lymph nodes and a high ploidy level found to be associated with tumors having a negative estrogen receptor. When the tumors were divided into a diploid group and an aneuploid group, the diploid group showed a significantly better prognosis than the aneuploid group, in 6-year survival. Similarly, the groups in which SPF was less than 20.0 per cent had significantly better prognoses than the group in which SPF was 20.1 per cent or more. These prognostic factors were evaluated with Cox's proportional hazard model and a significant correlation observed in lymph node status, ER status, ploidy level and S-phase fraction. It was thus concluded that ploidy level and SPF are important and independent prognostic factors for predicting the postoperative course of breast cancer patients.     

DNA ploidy pattern and tumour spread in gastric cancer

The DNA ploidy pattern of gastric cancer was studied in 58 patients to investigate the heterogeneity between primary tumour and metastases. In both primary tumours and lymph node metastases, diploid patterns accounted for 33 per cent, whereas all liver metastases were aneuploid. The percentage of polyploid cells was higher in the liver metastases than in primary tumours and lymph node metastases. When the heterogeneity of DNA ploidy pattern between primary tumour and metastasis was evaluated, diploid tumours had a significantly lower rate of lymph node metastasis heterogeneity than aneuploid tumours. When the DNA ploidy pattern and survival were evaluated, the patients who had a diploid pattern in both primary tumour and metastasis had a significantly higher survival rate than the patients who had an aneuploid pattern in the primary tumour and metastasis (57 per cent versus 26 per cent at 5 years). These data suggest that cell heterogeneity is a common phenomenon in gastric cancer, and this may be important in the evolution of the disease. Furthermore, the role of the DNA ploidy pattern as a prognostic factor is emphasized.     

Prognostic significance of flow cytometric DNA analysis in colorectal cancer

Significance of flow cytometric DNA analysis for assessing malignant potential and survival of colorectal cancer was investigated using paraffin-embedded materials from 144 patients with primary colorectal cancer who had been treated from 1971 to 1985. Forty-four percent of colorectal cancer were composed of diploid and 56 percent were aneuploid. DNA indices (DI) of aneuploid tumors showed a bimodal distribution. There was no significant correlation between ploidy pattern and clinicopathological factors. While, DI level showed significantly higher in poorly differentiated adenocarcinomas and in clinicopathological stage III and V tumors. Overall survival in the patients with aneuploid tumor was significantly worse than that in those with diploid tumor (p less than 0.001). Survival rate was poorer in the patients with aneuploid tumor than in those with diploid tumor, who were stratified according to categories of curable resection, stage, histological type, negative peritoneal or hepatic involvement and negative node metastases. However, there was no significant relation between DI and survival among the patients with aneuploid tumor. From these results, it was concluded that the nuclear DNA content of colorectal cancer may represent biological malignant potential of the disease, and that the DNA ploidy pattern may be an important prognostic indicator, being independent of clinicopathological factors.     

Metastatic mode and DNA ploidy in gastric carcinoma

We studied the amounts of nuclear DNA in gastric cancer metastases histologically and cytochemically by flow cytometry, which was performed retrospectively on paraffin-embedded specimens from 95 patients. At surgery, all cases of aneuploid cancer were positive for lymph node metastases. Liver metastases were frequently seen in aneuploid cancer (63%, P<0.01), while lung metastases were the most common in diploid cancer (50%, P<0.05). The incidence of peritoneal metastasis was high in undifferentiated diploid cancer (72%, P<0.01). Local lymph node recurrence after surgery was more common in aneuploid than in diploid cancer (P<0.01). The incidence of bone and distant lymph node metastasis was found to be strongly dependant on tissue differentiation. The DNA ploidy pattern is thus considered to be closely linked to lymph node, liver, and lung metastases in gastric cancer.     

Malignancy in gastric carcinoma, with special reference to the DNA ploidy and proliferative activity

Analysis of DNA ploidy patterns was performed on 129 primary gastric cancers and the results correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid. There was no correlation between DNA ploidy and histologic type. In aneuploid cancers, incidence of lymphatic invasion, lymph node metastasis and rate of advanced cases were significantly higher than those in diploid tumors. During the follow-up period of 5-10 years, 23 of the 40 patients (55%) with aneuploid tumors died of disease within 3-120 months. Only 13 of the 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) were from 2.8% to 26.7%, with a mean of 10.4%. There was no correlation between BrdU LI and histologic type or stage. The mean BrdU LI of early cancers was 8.1%, of advanced cancers, 11.9%. BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancer was 6.0%, of aneuploid cancers, 11.9%. There was a good correlation between BrdU labeling indices and DNA ploidy patterns. These results indicate that determination of DNA ploidy patterns and growth fractions by BrdU labeling may be useful in the conjecture of prognosis of the patient and in the selection of patients from various modalities.     

Node negative breast cancer: the prognostic value of DNA ploidy for long-term survival.

The DNA content of breast tumours from 170 patients who presented between 1978 and 1980 was measured by flow cytometry. The relationship between tumour ploidy and disease outcome was assessed and its association with other prognostic factors evaluated. Compared with those with diploid tumours, patients with aneuploid tumours had significantly earlier relapse and shorter survival (P less than 0.0001). Tumour ploidy was strongly related to grade (P less than 0.001), but there was no significant association between DNA ploidy and c-erb-B-2 expression, lymph node status or tumour size. In lymph node negative and c-erb-B-2 negative patients, aneuploid tumours were associated with a poorer prognosis (P less than 0.001) than diploid tumours. Multivariate analysis showed that tumour ploidy gave independent information on disease free and overall survival. Tumour ploidy may be used as an independent prognostic variable in patients with breast cancer and it may be helpful in defining patients within the node negative or c-erb-B-2 negative groups likely to have a poor outcome who might benefit from adjuvant treatment.     

Tumor DNA content in resectable, primary colorectal carcinoma.

Tumor DNA content was measured in patients with colorectal carcinoma in order to determine whether tumor ploidy was a prognostic indicator independent of standard clinical and pathologic characteristics. One hundred forty-seven patients were analyzed who had their primary resectable colorectal carcinomas resected with curative intent from 1974 to 1981. Aneuploid colorectal cancers (i.e., tumors with abnormal DNA content) tended to be less well-differentiated, to invade the serosa or extend beyond, and to have lymph node metastases rather than diploid tumors (i.e., tumors with normal DNA content). A significantly increased rate of recurrent disease was demonstrated in patients with aneuploid tumors as opposed to those with diploid tumors (46.7% vs. 4.8%, respectively [p less than 0.001]). In addition, patients with aneuploid tumors exhibited a significantly decreased disease-free and overall survival in comparison with patients with diploid colorectal carcinomas. A Cox regression analysis demonstrated that tumor DNA content was the single most important factor in predicting recurrence or death from colorectal carcinoma.     

Prognostic indicators in invasive breast cancer

Tumor size and axillary lymph node involvement are the primary determinants of clinical course for most patients. Receptors for estrogen and progesterone are important additional prognostic factors for disease-free survival, overall survival, survival time after initial disease recurrence, and the likelihood of response to hormonal therapy. Histologic grading has merit as a prognostic factor, although poor reproducibility limits its broad application. Promising data have been emerging from the use of flow cytometry to analyze DNA content and proliferative rate. Patients with aneuploid tumors are more likely to have a shorter survival time than patients with diploid tumors. A high S-phase fraction also identifies a subset of patients at increased risk for early relapse. A combined index of ploidy and S-phase may be a more useful guide; together, diploidy and low S-phase identify a subgroup of node-negative patients at very low risk for disease recurrence. A number of oncogenes have been identified in breast cancer; amplification of the HER-2/neu gene or overexpression of the gene product may be an important prognostic indicator for node-positive patients.