Strong claudin 5 expression is a poor prognostic sign in pancreatic adenocarcinoma.

We investigated the expression of claudin 5 in 88 ductal adenocarcinomas of the pancreas. The results were correlated with patient prognosis, with claudin 5 expression in blood vessels, with the expression level of bcl2 and bax and with apoptosis. Claudin 5 expression was detected in 24 (38%) cases. It was not associated with tumour size or spread, but strong claudin 5 expression correlated with a worse survival (p = 0.005). Claudin 5 also associated with a higher extent of apoptosis and greater expression of bax protein. In the tumour vasculature, some vessels displayed a loss of claudin 5 expression. The presence of this loss was associated with tumour grade and the presence of nodal metastases (p = 0.02, p = 0.022, respectively). These results indicate that claudin 5 is upregulated in a proportion of pancreatic ductal adenocarcinomas. The association of strong claudin 5 expression with a worse survival is in line with some earlier reports indicating that this protein is involved with increased locomotion and more aggressive spread of carcinomas. The association of claudin 5 with apoptosis and bax might be due to stronger cellular kinetics found in such tumours. The loss of claudin 5 expression in the tumour vasculature points to a leaky vessel type; this might also ease the access of tumours to vessels and be reflected in its association with the presence of nodal metastases.

Feasibility of minilaparotomy versus laparoscopic cholecystectomy for day surgery: a prospective randomised study.

BACKGROUND AND AIMS: minilaparotomy (MC) and laparoscopic cholecystectomy (LC) are commonly applied surgical techniques in the management of symptomatic gallstone disease. Both techniques are used in day surgery patients, but to our knowledge MC and LC have not been compared in randomised trials as day surgery procedures. MATERIAL AND METHODS: in this randomised parallel group clinical trial we compared the suc-cess rate of day surgery of MC with that of LC in 60 consecutive patients with non-complicated symptomatic gallstones presented for elective surgery at the Kuusankoski District Hospital (n = 38) and the Kuopio University Hospital (n = 22). Twenty nine patients underwent MC and 31 LC. The patients' outcome was recorded up to four weeks after the operation. RESULTS: the success rate as a day surgery for MC was 66% (19/29) and that for LC 55% (17/31) with no difference between the two groups. Chronic cholecystitis, postoperative nausea and vomiting were significant variables associated with failure in day surgery. There was no difference between the two groups in operation time, perioperative bleeding, conversion to conventional open cholecystectomy (one with MC and three with LC), length of hospital stay or sick leave. Three patients developed superficial infection (two with MC and one with LC). One patient with conversion in the LC-group developed a common bile duct stricture and was readmitted at the 10th postoperative day. DISCUSSION: both MC and LC are feasible surgical techniques for day surgery. However, appropriate prevention and prompt management of established postoperative nausea and vomit-ing and careful patient selection are important aspects for success of short-stay approach. If there is a sign of chronic cholecystitis preoperatively, it might be considered as a contraindication for day surgery.

Blood Transfusions in Major Pancreatic Surgery: A 10-Year Cohort Study Including 1404 Patients Undergoing Pancreatic Resections in Finland.

BACKGROUND: Despite guidelines on blood transfusion (TF) thresholds, there seems to be great variation in transfusion policies between hospitals and surgeons. In order to improve and unify blood transfusion policies, the Finnish Red Cross Blood Service carried out a project concerning the optimal use of blood products (Verivalmisteiden optimaalinen käyttö) between 2002 and 2011. In this study, we determined the blood transfusion trends in major pancreatic surgery in Finland. METHODS: Initially, 1337 patients who underwent major pancreatic resections between 2002 and 2011 were classified into the TF+ or TF- groups. Centers were divided into high-, medium-, and low-volume centers. The blood transfusion trends and the trigger points for blood transfusions in these patients were determined. RESULTS: There were no differences between high-, medium- and low-volume centers in blood usage, trigger points or the use of reserved blood units after pancreatoduodenectomy or total pancreatectomy. However, the trigger points were lowered significantly during the study period at high-volume centers (p = 0.003), and a better use of reserved blood units was found in high- (p < 0.001) and medium-volume (p = 0.043) centers. In addition, a better use of reserved blood units was found in high-volume centers after distal pancreatectomy (p = 0.020). CONCLUSION: Although only minor changes in blood transfusion trends after pancreatoduodenectomy or total pancreatectomy were found generally, the lowering of the transfusion trigger point and the best use of reserved blood units during the study period occurred in high-volume centers.

Minilaparotomy cholecystectomy as a day surgery procedure: a prospective clinical pilot study.

BACKGROUND AND AIMS: In some studies minilaparotomy cholecystectomy (MC) has been shown to be as good as laparoscopic cholecystectomy (LC) in the surgical treatment of cholecystolithiasis. To our knowledge, the MC operation is rarely considered as a day surgery procedure. PATIENTS AND METHODS: Thirty elective symptomatic non-complicated patients were included in the study during the end of the year 2004 to June 2005. The mean age of patients was 52 years (range 27-68), the mean body mass index 29 kg/m2 (range 19-41). Gallstones were confirmed with ultrasound and the preoperative liver laboratory tests were normal in all patients. A five (+/-2) centimetre-long incision was used avoiding to split the rectus abdominis muscle. All patients were re-evaluated four weeks postoperatively with the follow-up letter. RESULTS: The average operating time was 51 minutes (range 30-105 minutes). Day surgery was possible in 25 cases (83%). Five patients (17%) stayed over night at the hospital. There were four (13%) conversions to conventional cholecystectomy. The average postoperative sick leave was 16 days (range 14-30). Two patients returned to hospital. One patient had wound pain, but no complication was found, and the patient was not admitted. One patient had a wound infection and spent 6 days in the hospital. Twenty-nine (97%) patients were satisfied with the operation and were ready to recommend it for other patients. CONCLUSIONS: The results of this study support the suitability of MC as a day surgery procedure, but a prospective randomised trial is needed to evaluate the relative advantages of MC and LC.

Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized study with special reference to obesity.

BACKGROUND: Minilaparotomy cholecystectomy (MC) has recently challenged the role of the laparoscopic approach (LC) for cholecystectomies. However, the situation is far from clear when operating times and recovery are evaluated. METHODS: Altogether 157 patients with uncomplicated symptomatic gallstones were randomized into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of age, body mass index, American Society of Anesthesiology (ASA) physical fitness classification, and operating surgeon. RESULTS: The mean operating time was 55 +/- 19.5 min in the MC group and 79 +/- 27.0 min in the LC group (p < 0.0001). The postoperative hospital stay and length of sick leave did not differ between the two groups. There were no significant differences in postoperative pain, analgesic consumption, or postoperative pulmonary function between the groups. The body mass index did not influence operating time or patient recovery in either group. No major complications occurred in either groups. CONCLUSION: The MC procedure seems to be a faster technique than the LC approach for noncomplicated gallstone disease, with no difference in recovery times. The MC procedure also seems to be suitable for the obese patient.

Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer.

Hyaluronan (HA) is a linear high molecular weight extracellular polysaccharide. It is thought to be involved in mitosis and the enhancement of wound healing, tumor invasion, and metastasis. Because its clinical relevance in cancer has not been explored, we scored HA in colorectal adenocarcinoma and studied its relationship with patient survival. A specific probe prepared from cartilage proteoglycan aggregates was used to stain paraffin-embedded tumor samples from 202 colorectal adenocarcinoma patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the percentage of HA-positive carcinoma cells (HA%) and HA intensity in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Ninety-three % of tumors had at least a proportion of carcinoma cells positive for HA. HA intensity in tumor epithelium was stronger in Dukes' stages C and D tumors and in high-grade tumors. The cancer-related survival rate was lower among patients with strong HA intensity in tumor epithelium (P < 0.001) and high HA% (P < 0.001). Recurrence-free survival was also shorter in patients with an intense signal for HA (P = 0.001) and high HA% in tumor epithelium (P = 0.04). HA intensity in tumor epithelium independently predicted survival and recurrence-free survival (Cox's analysis). We conclude that a high proportion of HA-positive cancer cells and high intensity of the HA-signal predicts a poor survival rate. The abnormal expression of HA in the neoplastic colon epithelial cells is suggested to provide a distinct advantage for invasive growth and metastasis.

Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma.

PURPOSE: The transcription factor, activator protein (AP)-2, a 52-kd DNA-binding protein, is suggested to inhibit tumor growth through the activation of p21. To test this hypothesis, we analyzed AP-2 and p21 protein expressions in stage I cutaneous malignant melanomas to clarify their significance with regard to tumor progression and survival. PATIENTS AND METHODS: A consecutive series of 369 clinical stage I cutaneous malignant melanoma patients were investigated using immunohistochemistry. The detected expression levels were correlated with each other, with clinicopathologic data, and with melanoma survival. RESULTS: The loss of AP-2 expression was significantly associated with low p21 expression (P=.007), high tumor thickness (P=.001), high Clark's level (P=.046), high tumor-node-metastasis (TNM) category (P=.006), recurrent disease (P=.001), and male sex (P=.03). Tumor thickness, Clark's level, TNM category, bleeding, AP-2 index, and sex were all important predictors of both recurrence-free survival (RFS) and overall survival (OS) of melanoma in this order. In Cox's multivariate analysis, high tumor thickness (P=.0001), low AP-2 index (P=.0153), and bleeding (P=.0143) predicted poor RFS. Poor OS was predicted by high tumor thickness (P=.0008) and bleeding (P=.0092). CONCLUSION: The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma.

Population-based molecular detection of hereditary nonpolyposis colorectal cancer.

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.

Expression and prognostic value of alpha-, beta-, and gamma-catenins indifferentiated thyroid carcinoma.

Catenins (alpha, ss, and gamma) are a group of intracellular cell adhesion molecules that unite cytoskeleton with extracellular adhesion system. Abnormal expression of these molecules may have prognostic relevance in various carcinomas, including differentiated thyroid carcinoma (DTC). We have, therefore, evaluated the prognostic value of alpha-, ss-, and gamma-catenins along with traditional risk factors in 206 consecutive DTC patients by immunohistochemistry. Papillary carcinomas showed normal staining pattern for alpha-, ss-, and gamma-catenins in 124 (60%), 136 (67%), and 94 (46%) cases, respectively. Follicular carcinomas expressed alpha-, ss-, and gamma-catenins normally in 16 (48%), 18 (55%), and 8 (32%) cases, respectively. Follicular type of tumor showed more often reduced staining for all catenins than papillary carcinoma (P: = 0.009, P: = 0.004, and P: = 0.002, respectively). Age (>60 yr) and pTNM-stage were related to reduced alpha- and ss-catenin expression levels (P: = 0.027 and P: = 0.026, respectively) and larger size of the tumor to reduced ss- and gamma-catenin expressions (P: = 0.039 and P: = 0.007, respectively). Nodal metastases at the time of primary treatment related to reduced alpha-catenin expression and distal metastases to reduced ss- and gamma-catenin staining signals (P: = 0.022, P: = 0.014, and P: = 0.039, respectively). Reduced alpha-catenin associated with tumor recurrence (P: = 0.002) and reduced ss-catenin with cancer-related mortality (P: = 0.005). The multivariate analysis for recurrence-free survival showed that alpha-catenin and serum thyroglobulin level 1 yr after primary treatment were prognostic of recurrent disease (hazards ratio, 3.42, P: = 0.022; and hazards ratio, 10.03, P: = 0.0001). In addition, alpha-catenin retained its prognostic significance in low-stage patients (P: = 0.0151). We propose that the evaluation of alpha-catenin expression by immunohistochemistry in DTC patients has prognostic value in addition to that obtained by traditional prognostic factors.

Steroid metabolism gene CYP17 polymorphism and the development of breast cancer.

The potential role of the polymorphism in the CYP17 gene was evaluated in a case-control study with 483 incident breast cancer patients and 482 population controls, all of homogenous Finnish origin. Our data disagree with the earlier suggestions that the minor A2 variant of CYP17 would pose an increased risk for developing advanced breast cancer. In contrast, a tendency of inverse association was found for premenopausal women carrying the A2 allele containing genotypes with a multivariate adjusted odds ratio of 0.58 approaching statistical significance (95% CI, 0.31-1.07). Agreeing with previous observations, the protective effect of later age at menarche (> or =13 years) was mainly limited to women with A1/A1 genotype, although this could only be seen in premenopausal women (odds ratio, 0.34; 95% CI, 0.15-0.76). Similarly, we found a remarkably lower risk for premenopausal women with at least one child (odds ratio, 0.22; 95% CI, 0.07-0.62) to be mainly attributable to the A1/A1 genotype. CYP17 genotypes may thus modify individual breast cancer proneness in certain subpopulations, although they appear not to have any major modifying role in the risk of this malignancy overall. Because these findings are based on relatively small numbers in stratified analysis, they should, however, be interpreted with caution before being confirmed in future studies.

Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer.

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.

Polymorphic catechol-O-methyltransferase gene and breast cancer risk.

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genotype in individual susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for breast cancer. When studied separately by menopausal status, the COMT-L allele-containing genotypes were inversely associated with premenopausal breast cancer, especially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22-0.87). Among postmenopausal women a similar decreased risk was seen for local carcinoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31-0.98). The lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index (30 months) use of estrogen (OR, 4.02; 95% CI, 1.13-14.3), or with the COMT-L allele-containing genotypes and early age (

Expression of the tumour-associated antigen CA-242 in transitional cell bladder tumours: a comparison with CA-50.

The tissue expression of carbohydrate antigen CA-242 was analysed in formalin-fixed biopsy specimens from 147 transitional cell bladder tumours. The staining was related to established prognostic factors and survival during a mean follow-up of over 12 years and the staining results were also compared to expression of CA-50 antigen. Forty-one percent (60/147) of the tumours were negative for CA-242 and 59% (87/147) were positive. Normal bladder mucosa was positive for CA-242 and the umbrella cells in particular showed intense positive staining. In tumours, the umbrella cells were usually positive (when present) and in tumour tissue, positive cells appeared either as individual positive cells or in groups. None of the tumours was entirely positive for CA-242. The tissue expression of CA-242 could not be significantly related to TNM classification, papillary status, WHO grade or quantitative variables (DNA ploidy, S phase fraction, mitotic frequency, nuclear factors). The tissue expression of CA-242 was significantly weaker than the expression of CA-50. The expression of CA-242 was related to favourable prognosis in survival analysis (P = 0.04). The results show that the expression of the novel tumour marker antigen CA-242 as determined in paraffin-embedded material is a weak prognostic factor as compared with established prognostic factors in transitional cell bladder tumours.

Prediction of superficial bladder cancer by histoquantitative methods.

A retrospective clinicopathological study was done of 136 T1 bladder cancer patients, mean follow-up 10 years. With interactive morphometry, mean nuclear area, mean standard deviation of nuclear area (SDNA) and the mean area of the 10 largest nuclei (NA10) were measured in biopsy specimens from primary tumours. Volume corrected mitotic index (M/V index) was estimated in the same sections. Histological grading was done according to WHO and clinical staging according to UICC. Progress in bladder cancer was observed in 26 cases. Progressing tumours had significantly higher M/V values (P = 0.0038) than tumours without progression. By chi 2 statistics NA10 (P = 0.0065) and high M/V index values (P = 0.0104) eventually metastasised. Nuclear area (P = 0.0025), NA10 (P = 0.0053), histological grade (P = 0.0071), NA (P = 0.0563) and M/V index (P = 0.0979) predicted bladder cancer-related survival, in that order. The recurrence rate or recurrence-free period were not related to histological indices. The results suggest the use of these morphometric features instead of histological grading in the prediction of T1 bladder tumours.

Progression and survival in transitional cell bladder cancer: a comparison of established prognostic factors, S-phase fraction and DNA ploidy.

DNA flow cytometric (FCM) data, histological features and clinical stage of bladder tumours in 222 patients were related to outcome during a mean follow-up of 10 years. Aneuploidy was detected in 82 (37%) of tumours and 140 (63%) were diploid. Intratumour heterogenity of DNA ploidy was found in 27% of 30 cases. Aneuploidy and high S-phase fraction (SPF) were related to clinical stage, histological grade and papillarity (P less than 0.0001). Aneuploidy (P less than 0.0001) and high SPF (P less than 0.0001) predicted metastasis to pelvic lymph-nodes and to distant sites. T category (P less than 0.0001), SPF (P less than 0.0001), histological grade (P less than 0.0001), papillarity (P = 0.0021), DNA aneuploidy (P = 0.0094) and G2 fraction (P = 0.0340) predicted cancer-related survival. Multivariate analysis showed DNA aneuploidy as the most important predictor of progression in T category (P = 0.0003) and T category was the most important predictor of lymph-node involvement (P = 0.0083) and metastasis (P = 0.0015), followed by FCM parameters. In Ta-T1 tumours SPF predicted progression independently (P = 0.0153). FCM offers more accurate prognostic information in Ta-T1 tumours than conventional methods. In invasive tumours, FCM offers quantitative prognostic information in terms of pelvic lymph-node metastasis and metastasis to distant sites.

The role of nucleolar organiser regions as prognostic factors in breast cancer.

Nucleolar organiser regions (NORs) were stained in paraffin-embedded biopsy specimens of 80 female breast carcinomas by the silver (Ag) technique. The patients were prospectively followed up for a mean of 12.4 years (range 11.5-13.3). The number of different types of Ag-NORs was correlated with the histological grade, clinical stage, DNA ploidy, S-phase fraction (SPF) and clinical outcome. Grade III tumours showed higher Ag-NOR counts than low grade tumours. The total number of Ag-NORs (P = 0.0059) and the number of dispersed Ag-NOR (P = 0.0199) were significantly related to DNA ploidy aneuploid tumours showing higher Ag-NOR counts. The number of aggregated Ag-NORs was predictive (P = 0.0413) for the development of metastatic disease during follow-up. On the other hand, crude, cancer-related or recurrence-free survival could not be predicted significantly by the Ag-NORs. The results suggest that the number of Ag-NORs is clearly related to the proliferative activity in breast cancer, but the prognostic value of Ag-NOR counting is inferior to the previously recognised prognostic factors.

Prediction of superficial bladder cancer by nuclear image analysis.

A cohort of 270 superficial transitional cell bladder tumours (Ta-T1) was followed-up for over 8 years. WHO grade, papillary status and six nuclear factors were related to progression, recurrence-free survival (RFS) and bladder cancer-related survival (BS) during the follow-up period. Mean nuclear area (NA), standard deviation of nuclear area (SDNA), nuclear perimetry (PE), standard deviation of nuclear perimetry (SDPE), shortest nuclear axis (Dmin) and longest nuclear axis (Dmax) were significantly related to WHO grade and papillary status (P < 0.0001). All the nuclear factors were related significantly to progression in univariate analysis (P < 0.01) whereas in a multivariate analysis WHO grade (P < 0.0001) and papillary status (P = 0.048) included independent prognostic information. RFS was related to PE (P = 0.009), SDPE (P = 0.013), Dmin (P = 0.021), Dmax (P = 0.028) and SDNA (P = 0.029). In papillary tumours SDPE (P = 0.007) and Dmin (P = 0.024) predicted RFS. BS was related to WHO grade, papillary status, NA, SDNA, PE, Dmax, Dmin (all P < 0.0001) and to SDPE (P = 0.003). In papillary tumours PE (P < 0.0001), Dmax (P = 0.0022), Dmin (P = 0.0027), WHO grade (P = 0.0036), NA (P = 0.0005), SDNA (P = 0.0355) and SDPE (P = 0.0718) predicted BS. In multivariate analysis SDPE (P = 0.029) predicted RFS and survival was related to WHO grade (P < 0.001) and PE (P = 0.014) independently. In papillary tumours only Dmax (P = 0.001) predicted survival independently. The results show that superficial papillary transitional cell bladder tumours can be efficiently categorised into prognostic groups by nuclear image analysis and the results provide a new classification system for superficial papillary bladder tumours. Tumours with high nuclear factor values should be considered for radical primary therapy and adjuvant therapy after transurethral resections.

Tumour infiltrating lymphocytes as an independent prognostic factor in transitional cell bladder cancer.

The prognostic value of tumour infiltrating lymphocytes (TIL) was assessed in a cohort of 514 patients with a transitional cell bladder cancer (TCC) during a follow up period of over 9 years. The density of TIL were positively correlated to WHO grade (P < 0.0001), non-papillary growth architecture (P < 0.0001), morphometric nuclear factors (P < 0.007) and volume corrected mitotic index (M/V index) (P < 0.0001). Dense TIL predicted progression in Ta-T1 tumours (P < 0.0006) whereas in a multivariate analysis they had no independent predictive value. Dense TIL were related to short recurrence-free survival in Ta-T1 tumours in a univariate analysis (P = 0.06) as well as in a multivariate analysis (P = 0.005). Dense TIL predicted unfavourable prognosis in the entire cohort (P = 0.0316) and in papillary tumours (P = 0.062) whereas in nodular tumours TIL were a sign of good prognosis (P = 0.0141). Also in T3-T4 tumours TIL were related to less aggressive behaviour of TCC (P = 0.0259). In a multivariate analysis including clinical stage (T-category), WHO grade, papillary status, six morphometric nuclear factors and M/V index dense TIL were a highly significant indicator of a favourable prognosis (P = 0.007). Particularly TIL categorized rapidly proliferating TCC into prognostic groups (P = 0.001). The results show that TIL are a sign of efficient host defence mechanisms in TCC and TIL predict a favourable prognosis in invasive TCC.

Lymphocyte infiltrates as a prognostic variable in female breast cancer.

The predictive value of lymphocyte infiltrates (LI) was studied in 489 patients with breast cancer followed-up for over 10 years. LI were positively correlated to axillary lymph-node status, tumour diameter and histological and morphometric variables (P less than 0.001). In a multivariate analysis LI were independently related to axillary lymph-node status. LI predicted recurrence-free survival (RFS) in rapidly proliferating tumours (P = 0.0269). LI predicted RFS (P = 0.08) and breast cancer related survival (BS) (P = 0.0164) in rapidly proliferating, axillary lymph-node negative tumours. In a multivariate analysis LI independently predicted BS (P = 0.08) in rapidly proliferating tumours. LI independently predicted BS in rapidly (P = 0.025) and slowly (P = 0.09) proliferating, axillary lymph-node negative tumours. If the tumours were not categorised according to proliferation rate, LI and outcome were not significantly related. The results clearly confirm the presence of efficient immunological antitumour defence mechanisms in human breast cancer. Consequently tumour-host interactions are subject to further studies particularly in axillary lymph-node negative breast cancer.

Prognostic factors in axillary lymph node-negative (pN-) breast carcinomas.

Axillary lymph node-negative (pN-) breast carcinomas (n = 281) were analysed histoquantitatively for two mitotic indexes (MAI, mitotic activity index; M/V, volume corrected mitotic index) and nine nuclear factors with special emphasis on disclosing prognostic factors during a follow-up of 12 years. The M/V index (P = 0.0018), tumour size (P = 0.0052), MAI (P = 0.0115) and histological grade (P = 0.0565) predicted the recurrence-free survival. MAI (P = 0.0007), M/V index (P = 0.0046), tumour size (P = 0.0133), histological grade (P = 0.0528) and S.D. of the nuclear perimetry (P = 0.07) predicted the disease-related survival. In Cox's analysis, MAI (P = 0.004), adjuvant therapy (P = 0.03) and tumour size (P = 0.09) predicted survival independently. Recurrence-free survival was related independently to nuclear perimetry (P less than 0.001), SD of nuclear area (P = 0.01) and MAI (P = 0.019) in Cox's analysis. In small (diameter less than or equal to 20 mm) tumours, S.D. of nuclear perimetry predicted recurrence-free survival (P = 0.03) in Cox's analysis. The results advocate the use of mitotic indexes and nuclear factors in place or in combination with conventional histological grading in predicting the survival and tumour recurrence in axillary lymph node-negative breast carcinomas.