Relationship between DNA ploidy and survival in patients with exocrine pancreatic cancer

The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). All patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneuploid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p less than 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival (p = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.     

Flow cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen in submucosal carcinoma of the esophagus

BACKGROUND/AIMS: The aim of this study was to examine the role of p53 gene and tumor proliferating activity using anti-proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma (SCC) of the esophagus with invasion restricted to the submucosa. Their DNA contents and microscopic histopathological aspects were also studied. METHODOLOGY: Thirty-four submucosal SCC were studied histopathologically including immunohistochemical and flow cytometric analysis. RESULTS: DNA diploid was observed in 15 (44.1%) and DNA aneuploid in 19 (55.9%) cases. DNA ploidy patterns were relatively closely correlated with survival. Staining for the p53 product was positive in 61.8% of all cases. The average PCNA labeling rate (LR) was 55.9 +/- 16.7%. The incidence of lymph node metastasis was relatively higher in DNA aneuploid and high PCNA LR (> or = 50%) groups. There was, however, no significant correlation between p53 protein expression and lymph node metastasis. CONCLUSIONS: Our study suggests that DNA aneuploid and high PCNA LR are unfavorable characteristics and that p53 expression may not have a prognostic value.     

Prognostic impact of microsatellite instability and DNA ploidy in human colon carcinoma patients

BACKGROUND & AIMS: Genomic instability in colon cancers is a consequence of chromosomal instability characterized by aneuploidy or defective DNA mismatch repair (MMR) indicated by microsatellite instability (MSI). Given that high-frequency MSI (MSI-H) and diploidy are correlated, we determined whether they are independent prognostic variables. METHODS: Astler-Coller stage B2 and C colon cancers (N = 528) from patients treated in 5-fluorouracil-based adjuvant therapy trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for hMLH1, hMSH2, and p53 proteins was performed. DNA ploidy was analyzed by flow cytometry. Associations with disease-free and overall survival were determined. RESULTS: MSI-H was detected in 95 tumors (18%), and 70 (74%) of these were diploid. Tumors showing MSI-H (hazard ratio, 0.65; 95% confidence interval, 0.44-0.96; P = .023) or loss of MMR proteins (P = .024) were associated with better overall survival. Improved disease-free and overall survival were found for diploid versus aneuploid/tetraploid tumors (overall survival: hazard ratio, 0.59; 95% confidence interval, 0.43-0.79; P = .0003). In the subgroups of MSI-H and microsatellite stable (MSS)/low-frequency MSI (MSI-L) tumors, diploidy was associated with better survival. The prognostic impact of ploidy was similar in stage B2 and C tumors. Ploidy did not predict the benefit of 5-fluorouracil-based treatment. When ploidy, MSI, and MMR proteins were analyzed in the same multivariate model, only ploidy remained significant. CONCLUSIONS: DNA ploidy and MSI-H status were independent prognostic variables, yet ploidy was the strongest marker. Diploidy was associated with better survival in MSI-H and in MSS/MSI-L patient subgroups.     

Can endoscopic resection be applied for early stage ampulla of Vater cancer?

BACKGROUND: Although endoscopic resection can provide a wide tumor resection with a negative resection margin, it is not yet recommended as a curative therapy for ampulla of Vater cancer. METHODS: To investigate the microinvasion rate and the diagnostic accuracy of endoscopic biopsy to properly judge the safety of endoscopic resection for ampulla of Vater cancer. DESIGN: Single-center, retrospective study. SETTING: Academic medical center. PATIENTS: One hundred fifty-nine patients who were finally diagnosed with ampulla of Vater cancer after curative surgical resection. INTERVENTIONS: We surveyed the pathologic concordance rate of endoscopic biopsy and the surgical pathology. For the 36 early stage (Tis or T1) cancers, we surveyed the presence of microlymphovascular invasion, gross appearance (intra-ampullary type, periampullary type, or mixed type), and pathologic subtype (intestinal type or pancreaticobiliary type). MAIN OUTCOME MEASUREMENTS: Presence of microinvasion in early staged ampulla of Vater cancer. RESULTS: Endoscopic biopsy failed to reveal malignancy in 15.9% of the 126 cases. Microlymphovascular invasion was present in 17 cases (56.7%) of the 30 T1 cancers but was absent in all cases of the 6 Tis cancers (P = .02). Neither the gross appearance (P = .51) nor the pathologic subtype (P = .28) could predict the microinvasion rate. LIMITATIONS: Single-center, retrospective study with small number of patients. CONCLUSIONS: Although endoscopic resection improves the low predictability of endoscopic biopsy, surgical resection should be performed for the T1 stage ampulla of Vater cancer because of the high lymphovascular invasion rate. On the other hand, the safety of endoscopic resection should be evaluated by a large-scale study on Tis cancers to consider the absence of microinvasion.     

Prognostic value of flow cytometry in surgically treated primary gastric lymphoma.

AIM: To investigate whether flow cytometry could help to define the optimal therapeutic strategy of primary gastric lymphomas. MATERIAL AND METHOD: Retrospective study of 46 patients having primary gastric lymphoma--according to Dawson criteria--in Ann Arbor stage IE and IIE, who were surgically treated. From selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by flow cytometry (FC). Other pathological tumor features were analysed by hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any possible influence on postoperative survival was investigated through statistical analysis. RESULTS: The DNA ploidy pattern was diploid in 40 cases (87%) and aneuploid (hyperdiploid) in 6 (13%). Postoperative survival probability (PSP) was 62.7% at 5 years. Statistical analysis showed significant prognostic value for Ann Arbor classification--with higher PSP for stage IE (p = 0.009)--and FC parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors having S-phase (p = 0.044) or G2-M phase values (p = 0.023) under the respective mean values had higher PSP. No influence on PSP was found for wall invasion, Helicobacter pylori infection, Isaacson's histologic type or resection margin involvement. No significant relationship was appreciated between Isaacson's histologic type and DNA ploidy patterns. CONCLUSION: FC could be useful in assessing gastric lymphoma prognosis.     

Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis

BACKGROUND: Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. AIM: To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. METHODS: We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. RESULTS: Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis. CONCLUSIONS: Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.     

Diagnostic and prognostic value of peritoneal cytology in biliary tract cancer

BACKGROUND/AIMS: Evaluation of peritoneal cytology provides valuable prognostic information in abdominal cancers. The aim of this study is to assess the incidence and the prognostic value of conventional peritoneal cytology in biliary tract cancers. METHODOLOGY: A total of consecutive 41 patients with biliary cancers (17 bile duct, 20 gallbladder, 4 ampulla of Vater) underwent surgery between July 2003 and July 2005. Peritoneal cytology was performed in these patients at the beginning of laparotomy. On opening the abdomen, 100mL of normal saline were instilled into the subhepatic space and retrieved. Cytologic analysis was performed using the Papanicolau technique. RESULTS: The overall incidence of positive cytology findings was 9.8% (4/41). When analyzed by disease factors or stage, the prevalence of positive cytology was 0% in T1/T2, 6% in T3, 38% in T4 (p=0.03), 0% in N0, 25% in N1 (p=.03), 3% in M0, 27% in M1 (p=0.02), 0% in Stage I/II and 27% in Stage III/IV cases (p<0.01), respectively. Although survival was worse in patients with positive peritoneal cytology, when adjusting TNM stage the positive peritoneal cytology did not have significant prognostic value. CONCLUSIONS: Peritoneal cytology associates positively with advanced disease but does not increase prognostic information in biliary tract cancers.     

Cancer of the ampulla of Vater: results of a 20-year population-based study

BACKGROUND: Relatively little attention has been given to the epidemiology and management of cancer of the ampulla of Vater. SETTING: A series of 111 patients with a cancer of the ampulla of Vater diagnosed over a 20-year period (1976-1995) in a well-defined French population was used to analyse its incidence, management and prognosis as well as to determine time trends. Prognosis was determined by using crude and relative survival rates. Factors predictive of survival were also identified using a relative survival model in a multivariate analysis. RESULTS: Age-standardized incidence rates were 3.8 per 1000000 inhabitants in men and 2.7 per 1000000 inhabitants in women. Incidence increased over time in men from 1.9 during the first period (1976-1980) to 5.9 during the last period (1991-1995). In women, incidence rates remained stable. A resection for cure was performed in 52 cases (48.1%). Overall, 9.9% of these cancers were classified TNM stage I and 54.1% stage IV. There was no significant variation in treatment modalities and in stage at diagnosis over the study period. The overall operative mortality rate was 7.5%. Relative survival rates were 58.9% at 1 year, 30.9% at 3 years and 20.9% at 5 years. Five-year relative survival rates varied from 72.8% in TNM stage I cancers to 6.6% in TNM stage IV cancers. Age, treatment procedure and stage at diagnosis significantly influenced the prognosis of cancer of the ampulla of Vater. In a multivariate analysis, stage at diagnosis remained the major prognostic factor (P<0.01). CONCLUSIONS: Although its incidence is increasing in men, cancer of the ampulla of Vater remains a rare tumour in both sexes. No improvements in the management and care of patients have been achieved. Further studies are needed to enhance the understanding of this cancer.     

DNA content by flow cytometry in gastric carcinoma: pathology, ploidy and prognosis.

BACKGROUND/AIMS: The prognostic relevance of histopathologic findings in gastric carcinoma is well established. Studies on DNA-ploidy are still scanty and contradictory. METHODOLOGY: Histopathologic parameters, DNA ploidy and S-phase were evaluated in 78 cancer patients curatively resected, using formalin-fixed paraffin-embedded tissue. RESULTS: Thirty-nine tumors (50%) were aneuploid. No significant correlation was found between histologic data and ploidy, but tumors with nodal involvement were more frequently aneuploid. In univariate analysis, tumor location (p=0.05), tumor size (p=0.01), differentiation grade (p=0.02), Lauren classification (p=0.01), deeper infiltration of gastric wall (p=0.001), nodal affectation (p=0.0000) and number of lymph nodes (p=0.01), TNM stage (p=0.0000), type of gastrectomy performed (p=0.04), and DNA ploidy (p=0.04) significantly influenced survival. S-phase values had no effect on prognosis. In the multiple regression model, factors independently associated with survival were TNM stage (p=0.0009), nodal affectation (p=0.01) and, marginally, ploidy (p=0.08). CONCLUSIONS: In gastric carcinoma curatively resected, the more relevant prognostic factors were stage and nodal involvement. Fifty percent of the tumors were aneuploid. Aneuploidy was significantly associated with poorer prognosis.     

DNA ploidy and proliferating cell nuclear antigen in colonic adenomas and adenocarcinomas

To investigate the colonic adenoma-adenocarcinoma progression sequence, DNA ploidy analysis was performed on hyperplastic polyps to adenocarcinomas. DNA ploidy data were then compared with immunocytochemical staining for proliferating cell nuclear antigen (PCNA). In hyperplastic polyps to villous adenomas, all cases were diploid except one aneuploid villous adenoma. In three adenomas, diploidin situ adenocarcinomas were present. As diploid percentages decreased from hyperplastic polyps to villous adenomas, aneuploid percentages increased. In adenocarcinomas, the Dukes classification corresponded well to DNA ploidy status: all four stage A carcinomas were diploid, whereas three cases each of stage C1 and C2 carcinomas were aneuploid or multiploid. A surprising finding was that S-phase percentage in adenocarcinomas was not parallel with PCNA-positive tumor cell numbers. It is concluded that multistep adenoma-adenocarcinoma progression was partially reflected in DNA ploidy pattern from hyperplastic polyps to villous adenomas. In adenocarcinomas, the Dukes classification paralleled well the DNA ploidy status from stage A diploid to stage D aneuploid, but was not accompanied by increasing PCNA-positive cell numbers.     

DNA Flow Cytometry of Colorectal Carcinoma: Correlation of DNA Stemlines with Other Prognostic Indices

DNA flow cytometry (FCM) was performed on paraffin-embedded tissue blocks of 38 surgically resected colorectal carcinomas (CRC). Forty-seven percent of tumors exhibited aneuploidy and 53% were diploid. Seventy-two percent of patients in the aneuploid but only 35% in the diploid group were alive after a mean follow-up of 30.7 and 28.8 months (p = 0.01), and 5-yr survival of 56.7% and 11.7%, respectively (p less than 0.05). The site of tumor location, Dukes' stage, and serum CEA level did not predict a certain DNA stemline. However, irrespective of the ploidy pattern, a serum CEA level greater than 5.0 was associated with a higher mortality and poor 5-yr survival (p less than 0.005). Similarly, advanced Dukes' stage was associated with higher mortality (p less than 0.05). Forty-six percent of the patients with lesions that were Dukes' B2 or advanced stage received adjuvant therapy. Eighty-five percent of this subgroup of patients died; 18% of these patients had aneuploid tumors. The role of FCM in the assessment of prognosis of CRC deserves further clinical evaluation in a randomized control trial.     

Prognostic value of DNA ploidy patterns of colorectal adenocarcinoma

BACKGROUND/AIMS: The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been fully understood. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after resection. METHODOLOGY: We have prospectively collected tumor specimens from 420 patients with colorectal cancer since 1996. The DNA ploidy patterns were determined with the use of DNA flow cytometry. The correlation of DNA ploidy pattern and various characteristics of tumors and the prognostic significance of DNA ploidy patterns were evaluated by univariate as well as Cox's proportional hazard model. The disease-free survival curves were calculated with Kaplan-Meier's analysis, and the survival difference was determined by log-rank test. RESULTS: DNA ploidy patterns were diploid in 115 (27.4%) and aneuploid in 305 patients (72.6%). The pattern of DNA ploidy did not correlate with age, gender, location, differentiation, and stage of the tumors. In 146 patients who were followed up for at least 2 years, the disease-free survival curves were similar between the diploid and aneuploid group. Multivariate analysis disclosed that tumor staging was associated with the survival of patients but the DNA ploidy pattern had no prognostic significance. CONCLUSIONS: The DNA ploidy pattern was not a significant prognostic factor in short-term follow-up.     

Carcinoma of the ampulla of Vater: results of surgical treatment of a single center

BACKGROUND/AIMS: The aim of this study was to retrospectively evaluate our experience with ampulla of Vater tumors at the Creighton University and to establish the role of curative pancreaticoduodenectomy on the long-term survival rate of patients. METHODOLOGY: Between 1975 and 1997, 21 patients (15 M, 6 F) with ampulla of Vater tumors were identified using our tumor registry database. The mean age at diagnosis was 74 years (range 45-85). Family history of other types of cancers was positive in 11 patients. The two most common presenting symptoms were painless jaundice (75%) and abdominal pain (31%). RESULTS: Thirteen patients (62%) underwent curative pancreaticoduodenectomy and eight patients (38%) underwent palliative biliary bypass procedures. Pathological staging of thirteen pancreaticoduodenectomy patients included stage I, 5 patients; stage II, 1 patient; stage III, 2 patients and stage IV, 5 patients. There were nine patients with NO disease and 4 patients with N1 disease. The Kaplan-Meier analysis revealed significant survival benefit for pancreaticoduodenectomy patients (69.9 months) compared to the palliative procedure (4.8 months). Furthermore NO patients had a far better survival (69.9 months) compared to N1 patients (5.9 months) although this difference was not significant. There were no operative mortalities. CONCLUSIONS: Radical surgery such as pancreaticoduodenectomy seems to confirm long-term survival in patients with ampulla of Vater tumors especially when no nodal or distant metastases are present at the time of surgery. An aggressive approach, therefore, in such patients is justifiable.     

Expression of hedgehog proteins in periampullary cancer]

BACKGROUND/AIMS: Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma. METHODS: We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%). RESULTS: All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001). CONCLUSIONS: Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.     

DNA ploidy study of resected hepatocellular carcinoma in cirrhotic liver

Background/Aims: Results of several studies on DNA ploidy as a prognostic indicator in hepatocellular carcinoma are contradictory. The present study analysed the correlations between DNA ploidy of resected hepatocellular carcinoma and tumour characteristics, tumour recurrence, risk factors and survival.Methods: Tumoural DNA ploidy of hepatocellular carcinomas from 37 patients with cirrhosis who underwent curative tumour resection was studied by flow cytometry.Results: A diploid pattern was found in 23 hepatocellular carcinomas (62.2%) and an aneuploid pattern in 14 (37.8%). The tumour recurrence rate did not differ statistically between diploid (69.6%) and aneuploid (50%) hepatocellular carcinomas. The only prognostic variable with significant difference in DNA pattern was the histologic tumour type; the majority of non-trabecular tumours were aneuploid while most trabecular hepatocellular carcinomas had a diploid DNA pattern. Actuarial survival at 1, 2, 3 and 4 years of patients with diploid and aneuploid tumours was 69.6%, 40.6%, 16.2% and 0%, and 69.3%, 59.4%, 49.5% and 32.9%, respectively (log rank p=0.1927).Conclusion: These results indicate that DNA ploidy has no prognostic value in hepatocellular carcinoma.     

Influence of preoperative radiotherapy on DNA ploidy in squamous cell carcinomas of the oesophagus.

The influence of preoperative radiotherapy on the prevalence of DNA aneuploidy and the prognostic significance of tumour DNA ploidy was evaluated in 126 patients with squamous cell carcinoma of the oesophagus. Preoperative radiotherapy with 30 Gy was performed in 52 patients. DNA ploidy was analysed by flow cytometry on nuclei isolated from paraffin embedded tumour tissue. DNA aneuploidy was identified in 75 tumours (61%) and found to correlate significantly with tumour stage. The percentage of aneuploid carcinomas was significantly reduced by preoperative radiotherapy (surgery only group, 71%; radiotherapy group, 47%, p = 0.01). Although the median survival time was slightly better in the diploid than in the aneuploid group (11.3 and 8.0 months respectively), this difference was not statistically significant. A curative tumour resection was the most important prognostic factor. Preoperative radiotherapy did not prolong survival in oesophageal cancer.     

DNA index as a significant predictor of recurrence in colorectal cancer

PURPOSE: To clarify the prognostic significance of the DNA content in cases of colorectal cancer, we investigated the relationship between the DNA content, as determined by the DNA ploidy or DNA index, and disease-free survival. RESULTS: This study included 201 cases that were treated by curative surgery between 1989 and 1995 at our hospital. 68 were diploid and 133 were aneuploid. The mean DNA index of these tumors was 1.42. Recurrence occurred in 30 cases (14.9 percent). Tumor site, venous invasion, Dukes stage, DNA ploidy (diploid or aneuploid), and a DNA index (less than or greater than 1.4) correlated well with disease-free survival. A multivariable analysis suggested the DNA index to be a stronger predictor than DNA ploidy. Patients with aneuploid tumors had shorter disease-free survival than those with diploid tumors (P=0.011), especially in Dukes Stage C cases (P=0.0209). Patients with a DNA index greater than 1.4 also had a shorter disease-free survival than those with a DNA index less than 1.4 (P<0.001), especially in Dukes Stage C cases (P=0.0033). CONCLUSIONS: The DNA index value (less than or greater than 1.4) seems to be a stronger predictor than DNA ploidy (diploid or aneuploid), and the combination of Dukes stage, tumor site, and a DNA index is, therefore, considered to be clinically valuable in predicting recurrence in cases of colorectal cancer.Presented at the meeting of the Japanese Society of Gastroenterological Surgery, Yokohama, Japan, July 17 to 18, 1997.     

The clinicopathologic and immunohistochemical characteristics of ampulla of Vater carcinoma: the intestinal type is associated with a better prognosis

BACKGROUND/AIMS: We wanted to compare the clinicopathological parameters with the immunohistochemical expression patterns and patient survival for the intestinal type (IT) and the pancreatobiliary type (PT) of ampulla of Vater carcinoma. Ampulla of Vater carcinoma can be classified histologically into either IT or PT. The biologic behavior and patient prognosis vary considerably in relation to the tumor type. METHODOLOGY: From September, 1995, to February, 2004, 34 patients with the pathologic diagnosis of ampulla of Vater carcinoma were retrospectively reviewed and the prognostic factors were analyzed. To classify the phenotypes of the tumors, the keratin types (CK7 and CK20), the type of apomucin of the mucosa (MUC2), and the glucose transporter (GLUT1) were studied for differentiating the tumor types. RESULTS: The 5-year survival rate of the 34 patients with ampulla of Vater carcinoma was 58.8%. Histologically, 12 patients had IT and 22 had PT, and the IT patients all survived. The long-term survival after resection of the tumor was significantly greater for the patients with IT than for the patients with PT. Although these differences were not statistically significant, the prognosis of IT group seemed more favorable (p = 0.0955). On the immunohistochemical staining, MUC2 (p < 0.0001), CK20 (p = 0.0002) and CK7 (p = 0.0368) were statistically effective, but not GLUT1, for differentiating IT from PT. CONCLUSIONS: For the classification of the tumor phenotypes, performing immunohistochemical staining were helpful to differentiate the two types of tumor. A study with a larger number samples would probably elucidate the different clinical course between these two types of ampulla of Vater carcinoma.     

Microsatellite instability accounts for tumor site-related differences in clinicopathologic variables and prognosis in human colon cancers

OBJECTIVE:  Colon cancers with high frequency microsatellite instability (MSI-H) are preferentially located in the proximal colon. Given that 15–20% of sporadic colon cancers are MSI-H, we determined whether tumor site-specific differences in clinicopathological variables, biomarkers, and prognosis are due to inclusion of MSI-H cases.
METHODS:  TNM stage II and III primary colon carcinomas (N = 528) from patients enrolled in 5-fluorouracil-based adjuvant trials were analyzed for MSI using 11 microsatellite markers. Immunostaining for DNA mismatch repair (hMLH1, hMSH2, hMSH6) and p53 proteins was performed. DNA ploidy (diploid vs aneuploid/tetraploid) and proliferative indices (PI: S-phase + G₂M) were analyzed by flow cytometry.
RESULTS:  MSI-H was found in 95 (18%) colon cancers. Proximal tumors (N = 286) were associated with MSI-H, older age (>65 yr), poor differentiation, and diploid DNA content compared with distal tumors (all P ≤ 0.016). Nuclear p53 staining was more frequent in distal tumors ( P = 0.002); PI was unrelated to tumor site. When MSI-H tumors were excluded, no tumor site-related differences were found except for age, which remained associated with proximal cancers ( P = 0.030). Proximal site was associated with improved disease-free survival in all patients ( P = 0.042), but not when MSI-H cases were excluded ( P = 0.236). MSI-H status or loss of mismatch repair proteins, diploidy, and lower PI were associated with improved survival rates.
CONCLUSIONS:  Tumor site-related differences in clinicopathological variables, biomarkers, and prognosis of sporadic colon cancers can be explained by the inclusion of MSI-H cases. Older age, however, is associated with proximal tumor site independent of MSI status.     

Serum carcinoembryonic antigen and DNA ploidy in colorectal carcinoma. A prospective study.

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.