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Purpose: Predictive markers for risk stratification among patients with intrahepatic cholangiocarcinoma (IHC) are still lacking. Therefore, recent studies have focused on identifying the biological aspects of tumors that can provide more information about the tumor aggressiveness. The aim of this study was to prospectively evaluate the prognostic potential of the DNA index in patients undergoing liver resection for IHC. Methods: In a prospective long-term follow-up study, the DNA index of 65 IHC patients undergoing liver resection was assessed by DNA image cytometry, and this parameter, as well as standard histopathological parameters, correlated with the patient survival. Results: The mean DNA index was 1.69 ± 0.66 (range, 0.9-4.3). The univariate survival analysis showed that the DNA index ( p = 0.024) and tumor stage ( p = 0.017) were associated with patient survival, whereas all other standard histopathological factors had no predictive value. The multivariate analysis identified the DNA index ( p = 0.050) and tumor stage ( p = 0.028) as independent prognostic parameters. Conclusions: The DNA index is an independent predictive marker for IHC after liver resection. It is superior to most standard histopathological parameters and can be assessed pre- and postoperatively. Therefore, the DNA index might represent a promising tool in the decision-making process for patients with IHC. [ABSTRACT FROM AUTHOR]

To evaluate whether the combination of biological parameters increases their prognostic value, the expression of epidermal growth factor receptor (EGFR), DNA ploidy, and estrogen receptor (ER) status were analyzed on 998 patients with breast cancer. Poor findings for each biological parameter were positive for EGFR, aneuploid for DNA ploidy, and negative for ER. According to the number of poor findings in these three parameters, the groups with none (309 cases), one (377 cases), two (161 cases), and three (151 cases) poor findings were classified. A significant ( P < 0.0001) difference was found in the disease-free survival (DFS) among the four groups. A multivariate analysis indicated the combination of three biological parameters to be an independently significant factor for DFS, while the relative risk gradually increased as the number of poor findings increased. In conclusion, the present study indicated a gradual increase in the prognostic significance as the number of combined biological parameters increased. [ABSTRACT FROM AUTHOR]

Multiple tumors within the liver are a characteristic feature of hepatocellular carcinoma (HCC). This study investigated alterations in the histologic type and DNA content of multiple nodules of HCC. Both a pathologic examination and flow cytometric DNA analysis were performed on 49 resected specimens of multinodular HCC. The results showed that 35 cases had multiple metastatic satellite nodules around the main tumor (group 1), while 14 had two solitary nodules in different segments without satellite nodules (group 2). In group 1, 28 out of 35 (80.0%) showed a single DNA index while 7 (20.0%) revealed two different DNA contents in the main tumor. The histological type, cytological grade, and DNA index were equivalent between the main and satellite tumors in 100%, 88.6%, and 97.1% of the cases, respectively. In group 2, all tumors showed a single histological type, cytological grade, and DNA index in each nodule. The histological type was identical in 85.7% of the pairs of nodules, but the cytological grade and DNA index were different in 42.9% and 85.7%, respectively. The patients in group 2 showed a significantly higher 5-year survival rate than that in group I (64.8% vs 27.2%, P<0.05). This study thus indicates that the cytological grade and DNA content are useful in distinguishing multicentric occurrence from intrahepatic metastasis in HCC. [ABSTRACT FROM AUTHOR]

Venous invasion as a prognostic factor was evaluated in 124 patients with colorectal cancer. By classifying the patients as having either negative to mild invasion or moderate to marked invasion, a significant correlation was found between the degree of venous invasion and clinicopathological variables such as lymphatic invasion, lymph node metastasis, liver metastasis, and DNA ploidy. Significantly more favorable survival was seen in those with a lower degree of vascular invasion; however, of the six prognosticators analyzed by Cox's proportional hazard model, the only significant factors were depth of invasion and DNA ploidy. Although venous invasion showed no significance, it is still considered a valuable prognostic indicator that is easy and economical to perform. [ABSTRACT FROM AUTHOR]

We examined the p53 protein and human papilloma virus (HPV) by immunohistochemistry and DNA ploidy by cytofluorometry in paraffin-embedded esophageal carcinoma tissue specimens. Sixty-one patients with superficial esophageal carcinoma were operated on between 1983 and 1991 without any prior treatment. Immunostaining of the anti-p53 protein antibody (CM1) was positive in 32 carcinomas (52%). Patients with p53-positive tumors had a poorer outcome than those with p53-negative tumors ( P<0.05). In addition, patients with p53-positive tumors did not have any characteristic site of relapse. Only 5 of the 61 patients (8.2%) had HPV-positive tumors. One of these 5 carcinomas expressed both p53 protein and HPV. Three patients with HPV-positive tumors which had invaded the submucosal layer died of relapse. A determination of DNA ploidy revealed 30 patients with aneuploid tumors, 13 with polyploid tumors and 18 with diploid tumors. The outcome of the patients with aneuploid tumors was worse than that of the patients with diploid tumor ( P<0.05). p53 protein expression was not associated with DNA ploidy; however, the 16 patients who had both p53-positive and aneuploid tumors had a worse prognosis than patients with p53-negative and aneuploid tumors ( P<0.01). These findings suggest that p53 protein expression in conjunction with DNA ploidy may be a useful indicator in evaluating the prognosis of patients with superficial esophageal carcinoma. [ABSTRACT FROM AUTHOR]

The DNA ploidy and DNA indices (DI) of 414 patients with colorectal cancer were analyzed, and the incidence of patients with metachronous liver metastasis was found to be significantly higher in those with aneuploid tumors and a DI above 1.5 than in those with aneuploid tumors and a DI below 1.4, or in those with diploid tumors and a DI equal to 1.0. Next, to confirm the effectiveness of administering prophylactic portal infusion chemotherapy (PPIC) as adjuvant therapy for the prevention of metachronous liver metastasis in colorectal cancer, a randomized controlled trial of PPIC was performed on 110 consecutive patients with primary colorectal cancer who had undergone curative resection. Although the incidence of patients with metachronous liver metastasis in the two study groups was not significantly different at 3.3% in the PPIC group and 10.3% in the control group, the incidence in the patients with aneuploidy and a DI above 1.5 was significantly lower in the PPIC group than in the control group. These findings suggest that colorectal cancer with aneuploidy and a DI above 1.5 may have a strong tendency to metastasize to the liver, and that prophylactic portal infusion chemotherapy may be effective for preventing metachronous liver metastasis in such patients. [ABSTRACT FROM AUTHOR]

We report herein the rare case of a thymus carcinoid producing parathyroid hormone (PTH)-related protein (PTHrP) found in a 43-year-old Japanese man who presented with a 19-month history of dyspnea. The diagnosis of a carcinoid was established by light microscopic, electron microscopic, and immunohistochemical examinations. The tumor was considered to be thymic in origin because of its anatomic location, the presence of feeders to the tumor (derived from the internal thoracic arteries), and the fact that no other tumors from which it could have originated were found. After an excisional biopsy, which revealed PTH-related immunoreactivity in the tumor cells, 60 Gy of irradiation was delivered, resulting in a 48% reduction in the size of the tumor. Flow cytometry showed a diploid DNA pattern, with 94% of the cells in the GI phase, 4% in the S phase, 2% in the G2+M phase, and a G2+M/Gl ratio of 1.95. The primary cell culture showed some cells adopted in a cord-like pattern. To our knowledge, this is the first report of a carcinoid tumor in which positive staining for PTHrP by immunohistochemical methods was demonstrated. [ABSTRACT FROM AUTHOR]

To assess the prognostic value of DNA ploidy in colorectal cancer, compared with the histopathological findings, paraffin-embedded surgical specimens from 330 patients who underwent resection for primary adenocarcinoma were studied using a new modified method of flow cytometry. Of these specimens, 141 were DNA diploid and 189, DNA aneuploid, among which there were 3 DNA hypodiploid lesions. Of the ten variables studied in curative resection, DNA ploidy ranked fourth in prognostic significance according to the linear trend by the χ test, after nodal status, grade of cellular differentiation, and degree of invasive growth, if the DNA ploidy pattern was classified into three categories. Conversely, DNA ploidy was the sixth most significant factor if DNA hypodiploidy was included in the DNA aneuploidy. The Cox multivariate analysis showed that DNA ploidy was one of the five significant factors independently determining prognosis; however, if adjustment for the modified Dukes' stage was made by the Mantel-Haenszel test, the survival difference between the diploid and aneuploid groups did not reach a statistically significant level. Thus, we conclude that from a practical point of view, DNA ploidy is not an essential factor which must be combined with histopathological variables for a better prediction of patient outcome. [ABSTRACT FROM AUTHOR]

Immunohistochemical c- erbB-2 protein overexpression was detected in 34 of 124 (27.4%) paraffin-embedded breast cancer specimens. Although no difference was seen between the c- erbB-2 positive and negative groups in 5-year disease-free survival, 5-year overall survival was significantly less favorable in the c- erbB-2 positive group. Furthermore, patients graded as having positive c- erbB-2 staining and aneuploid DNA showed significantly poorer survival than those in other categories. The significant prognostic factors, determined by a multivariate analysis, were nodal status and c- erbB-2 overexpression. Our findings therefore suggest that c- erbB-2 expression is a prognostic factor in breast cancer and that it could be useful in the determination of postoperative adjuvant therapy. [ABSTRACT FROM AUTHOR]

Flow cytometric DNA analysis was performed on 45 neuroblastomas in order to evaluate the prognostic significance of DNA ploidy. The DNA ploidy was diploid in 14 and aneuploid in 31 neuroblastomas and did not correlate with the conventional prognostic variables such as age, Evans' stage, or the primary site of the tumor. The survival of 31 patients with aneuploid tumors was comparable to that of 14 patients with diploid tumors. On the other hand, DNA aneuploidy was associated with a decreased long-term survival in 21 patients older than 24 months of age at the time of operation, and in 27 patients with advanced disease at Evans' stage III or IV. These results suggest that more intensive and longer-term postoperative chemotherapy is necessary for neuroblastoma patients older than 24 months of age, or for those with advanced disease if they have aneuploid tumors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Paraffin-embedded tumor samples from 151 patients with stage I gastric cancer were analyzed by DNA flow cytometry, and 80 patients recieved an infusion of bromodeoxiurudine (BrdU) to determine S-phase fraction. S-phase fractions of tumors were measured by the immunohistochemical method using anti-BrdU monoclonal antibody. Of the 151 patients, 81 (54%), and 70 (46%) showed diploid and aneuploid patterns. There was no significant association between DNA ploidy and wall invasion, histologic type, or lymphatic invasion. Aneuploid tumors were associated with positive-vessel invasion. When the DNA ploidy and clinicopathological parameters were simultaneously entered into the Cox regression model, DNA ploidy and wall invasion emerged as independent prognostic parameters. Aneuploid tumors had significantly higher values of BrdU labeling indices than diploid ones. These results indicate that the determination of DNA ploidy patterns may be an important prognostic factor in patients with stage I gastric cancer, and may be useful in deciding the therapeutic schedule of patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Flow cytometric DNA content analyses were performed on samples from 72 patients with neuroblastoma. Nuclear suspensions obtained from paraffin-embedded samples were prepared using the method described by Schutte et al. Determination of DNA ploidy was possible in 62 out of 72 patients. DNA diploidy was detected in 23 (37.1%) and DNA aneuploidy was found in 39 (62.9%) of these 62 patients. Cell sorting was performed on two peak areas of the DNA histogram of samples with aneuploidy. The sorted cells of the first peak area were composed of small round cells and were considered to be normal lymphocytes. The sorted cells of the second peak area were composed of relatively large cells with obvious nucleoli and were considered to be neuroblastoma cells. Thus, two cell components could be distinguished by cell sorting. It is concluded that cell sorting may be of benefit in giving detailed information about DNA histograms, even in samples obtained from paraffin-embedded tissue. [ABSTRACT FROM AUTHOR]

DNA ploidy and expression of the c-myc oncoprotein p62 and the v-H-ras oncoprotein p21 were examined in 54 colorectal carcinomas. DNA ploidy, determined by DNA flow cytometry, was diploid in 19 samples and aneuploid in 35. Expression of the p62 oncoprotein, determined by immunohistochemical staining, was intensely positive in 18 samples while that of the p21 oncoprotein, also determined by immunohistochemical staining, was positive in 29. There was no correlation between DNA ploidy and expression of the p62 oncoprotein, and DNA ploidy did not correlate with expression of the p21 oncoprotein. There was, however, a close correlation between expression of the p62 oncoprotein and that of the p21 oncoprotein being P<0.01 according to Peason's chisquare test. [ABSTRACT FROM AUTHOR]