A Comparison of the Clinicopathological Features, Metastasis Sites and Survival Outcomes of Invasive Lobular, Invasive Ductal and Mixed Invasive Ductal and Lobular Breast Carcinoma.

OBJECTIVE: We compared the breast cancer patients with invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC) and mixed invasive ductal and lobular carcinoma (IDLC) in terms of clinicopathological and treatment features, metastatic patterns and long-term survival. MATERIALS AND METHODS: In a 10 years patient cohort, 3412 patients with unilateral breast carcinoma were enrolled in the study. Tumors were classified histologically according to criteria described by World Health Organization classification. RESULTS: The highest rate of T3 tumors were found in IDLC patients, the lowest in IDC patients, and the difference between groups was significant only in comparison of IDC vs IDLC. Axillary positivity rate was highest in IDLC, lowest in ILC; differences were significant in comparisons of IDLC vs ILC and IDLC vs IDC. There was no significant difference between the patient groups in terms of surgical treatment, mastectomy and breast conserving surgery. Rate of bone metastasis was highest in IDLC, lowest in IDC, with significant difference between IDLC and IDC. Locoregional recurrence-free survival (LRFS) rate was 90.9% in ILC patients, 92.5% in IDC patients, 92.9% in IDLC patients, with no significant difference between the groups; in multivariate Cox analysis, histological type had no prognostic significance (p=0.599). Distant metastasis-free survival (DMFS) rate was 66.2% in ILC patients, 66.7% in IDC patients, 57.1% in IDLC patients; in multivariate Cox analysis, histological type had no prognostic significance (p=0.392). CONCLUSION: Although these results suggest that IDLC may have a worse prognosis than IDC and ILC, in multivariate analysis LRFS and DMFS were not significantly different among the histological type groups.

Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance.

PURPOSE: The presence of prostate-specific antigen (PSA) in colon cancer tissues has been shown, but its clinical significance has not been known yet in colorectal cancer patients. We investigated the prognostic significance of percent free PSA value (free PSA/total PSA × 100) in female patients with colorectal cancer. METHODS: The serum concentrations of total and free PSA were measured by solid-phase two-site immunoradiometric assay in 184 patients. RESULTS: The cancer-specific survival (CSS) of patients with percent free PSA value ≥35 was significantly better compared to that of patients with percent free PSA value <35 (CSS rate was 82.9 and 55.5 %, respectively; log-rank x2 = 8135, p = 0.004). In multivariate Cox analysis, this percent free PSA threshold value had independent prognostic significance (relative risk 0.27, 95 % confidence interval 0.11-0.64, p = 0.003). CONCLUSION: Percent free PSA value, calculated by serum total and free PSA levels, has prognostic significance in women with colorectal cancer. The studies with larger patient series, utilizing ultrasensitive PSA assays whose lowest detection limit is lower, are required for a clearer understanding of this issue.

The prognostic value of the number of lymph nodes removed in patients with node-negative colorectal cancer.

BACKGROUND: To investigate the prognostic significance of the number of lymph nodes removed in colorectal cancer (CRC) patients with no metastatic lymph node. PATIENTS AND METHODS: The clinicopathological data of 461 CRC patients was analyzed. In order to compare the survival of patients who had fewer lymph nodes removed versus the survival of patients who had 1-3 metastatic lymph node(s), a separate group of 74 N1 disease patients were also included in the study. All patient data were collected prospectively. Kaplan-Meier method was used for calculation and plotting of the survival curves of the patient groups, and log-rank test was used for the comparison of the survival curves. RESULTS: Cancer-specific survival (CSS) rates of patients who had 1-7 lymph node(s) and 8-11 lymph nodes removed were significantly worse than those who had 12 or more lymph nodes removed (p = 0.006 and p = 0.037, respectively), while CSS was not significantly different between those who had 1-7 versus 8-11 lymph node(s) removed (p = 0.647); this grouping had independent prognostic significance in Cox analysis (p = 0.006). CSS of patients with N1 disease was not significantly different from those who had 1-7 and 8-11 lymph node(s) removed (p = 0.312 and p = 0.165, respectively), while it was significantly worse than CSS of patients who had 12 or more lymph nodes removed (p = 0.001). CONCLUSION: In colorectal cancer patients whose removed lymph nodes are non-metastatic, removal of at least 12 lymph nodes will determine the lymph node status reliably.

The impact of primary tumor resection on overall survival in patients with colorectal carcinoma and unresectable distant metastases: a prospective cohort study.

BACKGROUND: To compare the patients with primary colorectal carcinoma (CRC) and non-resectable distant metastases with or without primary colorectal tumor resection as a primary treatment in terms of postoperative mortality and overall survival (OS). PATIENTS AND METHODS: The clinicopathological data of 188 CRC patients with non-resectable distant metastases was analyzed. All patient data were collected prospectively. Colorectal tumor was resected in 121 patients (64.3%). Kaplan-Meier method was used for calculation and plotting of the OS curves of the patient groups, and log-rank test was used for the comparison of the survival curves. The relative importance of the prognostic features was investigated using the Cox proportional hazards model. RESULTS: In the whole series and in the patient group undergoing emergency surgical intervention, mortality rate was lower in patients having colorectal tumor resection compared with non-resected patients, with differences approaching the significance level (p = 0.072 and p = 0.076, respectively). Median OS time was significantly longer in resection group (11.0 months), compared with non-resection group (5.5 months) (p < 0.001); in the multivariate Cox analysis colorectal tumor resection had independent prognostic significance (p < 0.001). CONCLUSION: Resection of colorectal tumor in primary CRC patients with non-resectable distant metastasis gives significant survival advantage without increasing postoperative mortality compared with non-resection.

Axillary lymph node status and prognosis in multifocal and multicentric breast carcinoma.

According to tumor-node-metastasis classification, tumor size should be based only on the largest tumor for multifocal and multicentric (MFMC) carcinomas. We estimated tumor size of MFMC carcinoma using either largest dimension of the largest tumor (dominant tumor size) or sum of the largest dimension of all tumors (aggregate tumor size), and compared the risk of axillary lymph node metastasis and prognosis between MFMC and unifocal carcinoma. We retrospectively reviewed the file records of 3,616 patients with MFMC (258 patients, 7.1%) and unifocal (3,358 patients) carcinoma. In T1 and T2 tumor subgroups, using dominant (p = 0.001 and p < 0.001) and aggregate (p = 0.017 and p = 0.004) tumor size axilla-positivity ratio was significantly higher in MFMC carcinoma compared with unifocal carcinoma. In stage I and II disease classified according to either dominant or aggregate tumor size, there was no significant survival difference between MFMC and unifocal carcinoma patients. In patients with stage III disease by dominant and aggregate tumor size disease-free survival was significantly worse in MFMC carcinoma compared with unifocal carcinoma (p = 0.036 and p = 0.041); multifocality and multicentricity had no independent prognostic significance (p = 0.074 and p = 0.079). The risk of axillary metastasis in MFMC carcinoma was higher than unifocal carcinoma, regardless of the method employed for tumor size estimation. MFMC carcinoma staged according to either dominant or aggregate tumor size had similar survival with unifocal carcinoma. We recommend using the largest dimension of the largest tumor in estimation of tumor size for MFMC carcinoma.

Lymph node ratio may be supplementary to TNM nodal classification in node-positive breast carcinoma based on the results of 2,151 patients.

BACKGROUND: The aim of the present study was to determine how lymph node ratio (LNR; the ratio of the number of metastatic lymph nodes to the number of removed lymph nodes) can supplement the TNM nodal classification in breast carcinoma. METHODS: We retrospectively reviewed the file records of 2,151 patients. RESULTS: Lymph node ratio-based low- (LNR ≤ 0.20), intermediate- (LNR 0.21-0.65), and high-risk (LNR > 0.65) patient groups had significantly different disease-free survival (DFS) (P < 0.001). The DFS of patients with N1, N2, and N3 disease was significantly different (P < 0.001). When LNR and TNM nodal groupings were included together in the Cox analysis, both groupings had independent prognostic significance (P < 0.001 and P < 0.001, respectively). The most significant LNR threshold value separating patients in low-risk and high-risk groups in terms of disease recurrence was 0.20 for N1 disease (P < 0.001), 0.35 for N2 disease (P < 0.001), and 0.90 for N3 disease (P < 0.001). CONCLUSIONS: Lymph node ratio and TNM nodal groupings show no superiority over each other in categorizing patients with node-positive breast carcinoma into prognostic groups of low-, intermediate-, and high-risk. However, LNR grouping may supplement TNM nodal classification by categorizing patients within each TNM nodal group into low-risk and high-risk groups with significantly different survival.

Survival benefit of post-mastectomy radiotherapy in breast carcinoma patients with T1-2 tumor and 1-3 axillary lymph node(s) metastasis.

OBJECTIVE: To investigate the role of post-mastectomy radiotherapy in breast carcinoma patients with a tumor size of 5 cm or smaller (T1-2) and 1-3 axillary lymph node(s) metastasis (N1). METHODS: We retrospectively reviewed the file records of 575 patients receiving radiotherapy (452 patients) and not receiving radiotherapy (123 patients). RESULTS: In the whole series, locoregional recurrence-free survival was significantly better in patients receiving radiotherapy compared with patients not receiving radiotherapy (P<0.001); in the multivariate Cox analysis, radiotherapy had an independent prognostic value (P<0.001). In patients with a tumor size of 2 cm or less (T1), locoregional recurrence-free survival was significantly better in patients receiving radiotherapy compared with those not receiving radiotherapy (P=0.016). In the patient subgroup with a T1 tumor and a lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of removed lymph nodes) of 0.25 or less, there was no significant difference between the patients receiving and not receiving radiotherapy in terms of locoregional recurrence-free survival (P=0.071). In patients with a tumor size of 2.1-5 cm (T2), locoregional recurrence-free survival was significantly better for patients who received radiotherapy compared with those who did not (P=0.001). In patients with a T2 tumor and a lymph node ratio of ≤0.08, there was no significant difference in locoregional recurrence-free survival between the patients receiving and not receiving radiotherapy (P=0.645). CONCLUSIONS: Post-mastectomy radiotherapy is beneficial in reducing the locoregional recurrence risk in T1N1 breast carcinoma patients with a lymph node ratio of >0.25 and in T2N1 breast carcinoma patients with a lymph node ratio of >0.08. In patients with a lymph node ratio equal to or less than these ratios, post-mastectomy radiotherapy could be omitted to avoid radiotherapy-related risks.

Prognostic Significance of the Number of Removed and Metastatic Lymph Nodes and Lymph Node Ratio in Breast Carcinoma Patients with 1-3 Axillary Lymph Node(s) Metastasis.

We evaluated the prognostic significance of lymph node ratio (LNR), number of metastatic lymph nodes divided by number of removed nodes in 924 breast carcinoma patients with 1-3 metastatic axillary lymph node(s). The most significant LNR threshold value separating patients in low- and high-risk groups with significant survival difference was 0.20 for disease-free survival (P < 0.001), 0.30 for locoregional recurrence-free survival (P < 0.001), and 0.15 for distant metastasis-free survival (P < 0.001), and the patients with lower LNR had better survival. All three LNR threshold values had independent prognostic significance in Cox analysis (P < 0.001 for all three of them). In conclusion, LNR is a useful tool in separating breast carcinoma patients with 1-3 metastatic lymph node(s) into low- and high-risk prognostic groups.

The prognosis of tumors with only microscopic skin involvement without clinical T4b signs is significantly better than T4b tumors in breast carcinoma.

The number of studies forming a base for tumor (T)-node (N)-metastasis (M) classification by comparing T4b tumors with only histological skin involvement in breast carcinoma is limited and results are contradictory. In this study, the survival of patients with T4b tumor and patients whose tumor had only microscopic skin involvement without clinical T4b signs were compared. The file records of 101 patients with T4b tumor (group A) and 79 patients whose tumor had only microscopic skin involvement (group B) were reviewed. The endpoint was disease recurrence. For the whole series, disease-free survival (DFS) of group B patients was significantly better compared with group A patients treated with either adjuvant (p<0.001) or neoadjuvant (p<0.001) therapies. When patients were subgrouped according to tumor size, DFS of group B patients was significantly better than group A patients receiving either adjuvant or neoadjuvant therapy for all tumor size subgroups of ≤3, >3, ≤5, and >5cm. Presence of T4b clinical signs had independent prognostic value in multivariate Cox analysis. In conclusion, tumors with only histological skin involvement without clinical T4b signs should be classified as T1-T3 according to their size instead of T4 as stated in the TNM classification.

Is there any prognostically different subgroup among patients with stage IIIC (any TN3M0) breast carcinoma?

BACKGROUND: We investigated whether there are prognostically different subgroups among patients with stage IIIC (any TN3M0) breast carcinoma. METHODS: The file records of 348 female patients operated for stage IIIC breast carcinoma were reviewed. The endpoint was disease recurrence. RESULTS: Patients with a T1, T2 or T3 tumor had significantly better disease-free survival (DFS) compared to those with a T4 tumor. In the patient group with T1,2,3N3M0 disease, the DFS was significantly better in patients with between 10 and 15 metastatic axillary lymph nodes, compared to patients with 16 or more metastatic lymph nodes (p = 0.0360) and in patients with a nodal ratio ( number of metastatic lymph nodes divided by number of removed nodes) less than or equal to 0.80, compared to patients with a nodal ratio greater than 0.80 (p = 0.0003). In the patient subgroup with between 10 and 15 metastatic lymph nodes, those with a nodal ratio greater than 0.80 had significantly worse DFS, whereas in the patient subgroup with 16 or more metastatic lymph nodes the nodal ratio had no prognostic significance. The DFS of patients with 10 to 15 positive lymph nodes and a nodal ratio of up to 0.80 was significantly better than that of both the patients with 10 to 15 positive lymph nodes and a nodal ratio greater than 0.80 (p = 0.0002), and the patients with 16 or more positive lymph nodes (p = 0.0002); survival of the latter two patient groups was similar. CONCLUSIONS: Patients with T1,2,3N3M0 disease can be divided into prognostically different subgroups according to the number of metastatic lymph nodes in the axilla and the nodal ratio; in this way, different patient subgroups may be offered different treatment strategies.

CEA, CA 19-9, and CA 125 in the differential diagnosis of benign and malignant pancreatic diseases with or without jaundice.

BACKGROUND AND OBJECTIVES: In this study, the value of the serum tumor markers carcinoembryonic antigen (CEA), CA 19-9, and CA 125 was assessed in the differential diagnosis of benign and malignant pancreatic diseases with and without obstructive jaundice. METHODS: Serum levels of CEA, CA 19-9, and CA 125 were measured by immunoradiometric assay before the treatment in 123 patients with pancreatic carcinoma and 58 patients with a benign pancreatic disease. RESULTS: The sensitivity of CEA, CA 19-9, and CA 125 in the diagnosis of pancreatic carcinoma was 39.0%, 81.3%, and 56.9%; and specificity was 91.4%, 75.9%, and 77.6%, respectively. Although there was no significant difference between the CA 19-9 positivity ratios of the jaundiced (84.3%) and nonjaundiced (73.5%) patient subgroups of the pancreatic carcinoma, this ratio was significantly higher in the jaundiced subgroup (64.7%) than the nonjaundiced subgroup (7.3%) of the benign pancreatic diseases (P < 0.001). The CEA and CA 125 positivity ratios of jaundiced and nonjaundiced subgroups of patients with benign and malignant pancreatic diseases were not significantly different. CONCLUSIONS: In the differential diagnosis of pancreatic carcinoma from benign pancreatic diseases, CA 19-9 can be useful in the nonjaundiced patients, whereas CA 125 provides a limited contribution in jaundiced patients.

Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes.

BACKGROUND: The American Joint Committee on Cancer (AJCC) TNM classification for breast carcinoma had not been changed for 15 years, since the publication of the third edition in 1987. However, in the sixth edition, published in 2002, significant modifications were made with regard to the number of metastatic axillary lymph nodes. The authors investigated whether the sixth edition of the TNM classification provided more reliable prognostic information compared with the third edition. METHODS: The records of 1230 patients who underwent surgery for invasive breast carcinoma between 1993 and 1999 were reviewed. Each patient was assigned to axillary lymph node and disease stage groups according to the 1987 and 2002 AJCC TNM classifications. Disease-free survival (DFS) curves were calculated and plotted using the Kaplan-Meier method and the two-sided log-rank test was used to compare the survival curves of the patient groups. RESULTS: Of the 1067 patients who were classified as having Stages II and III disease according to the 1987 classification, 411 (38.5%) were shifted to higher disease stages using the 2002 classification. Among the 1987 Stage IIA, Stage IIB, and Stage IIIA patients, the DFS rates of the patients who were shifted to higher stages of disease were significantly worse than those of the patients for whom the stage of disease was not changed. Among those patients classified as having T4anyNM0 (Stage IIIB) disease according to the 1987 classification, there was no survival difference noted between those patients with T4N0,1,2M0 disease (who formed the Stage IIIB group) and those with T4N3M0 disease (who formed the Stage IIIC group) according to the new staging system. Of the 221 patients who formed the new Stage IIIC group, 12.2% were classified as having Stage IIA disease, 42.1% as having Stage IIB disease, 38.9% as having Stage IIIA disease, and 6.8% as having Stage IIIB disease according to the 1987 classification. The survival rates of these Stage IIA, Stage IIB, and Stage IIIA patients were not found to be significantly different; however, the survival of patients in the Stage IIIB group was found to be significantly worse than the survival of the patients in the other disease stage groupings, and the patients in the Stage IIIC group were not a prognostically homogeneous group. On the basis of these results, the authors placed patients with T4anyNM0 disease in the same group (Stage IIIB). When the 2002 classification was rearranged in this manner, patients with Stage IIIC disease formed a homogeneous group; the 5-year DFS rate of patients with Stage IIIB disease was found to be significantly worse than that for patients with Stage IIIC disease (P = 0.0011). CONCLUSIONS: In the 2002 TNM classification for breast carcinoma, patients with T4anyNM0 disease should form a distinct stage grouping and this stage grouping (Stage IIIC) should be placed before Stage IV, and Stage IIIB disease groupings should include patients with T1,2,3N3M0 disease. In this way, the authors hope that the 2002 AJCC TNM classification, which provides more reliable prognostic information than the 1987 classification, will become more refined.

The significance of perineural invasion as a prognostic factor in patients with gastric carcinoma.

PURPOSE: Few studies have investigated the prognostic significance of perineural invasion (PNI) in gastric cancer. Therefore, we examined the association between PNI and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. METHODS: Paraffin sections of surgical specimens from 354 patients who underwent gastric resection were stained with hematoxylin and eosin. PNI was assessed histologically as positive when cancer cells were seen in the perineurium or neural fascicles. Survival analysis was done in 219 patients with T(2,3,4) tumors who underwent potentially curative resection. Data were collected prospectively. RESULTS: PNI was positive in 211 of the 354 patients (59.6%). The ratio of undifferentiated tumors, tumors with vascular invasion, and lymph node metastasis was significantly higher in the PNI-positive patients than in the PNI-negative patients ( P < 0.0001 for all three associations). As the depth of mural invasion increased, so did PNI positivity ( P < 0.0001). The overall survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients in the univariate analysis ( P = 0.0009). However, PNI had no independent prognostic significance in the multivariate Cox proportional hazards model analysis. When the patients were separated into subgroups, PNI had prognostic value in patients with T(3) tumors ( P = 0.036) and no lymph node metastasis ( P = 0.005) in the univariate analysis, but no prognostic significance in the multivariate analysis. CONCLUSIONS: Although the incidence of PNI is high in gastric carcinoma and increases with the progression of disease, it does not provide any additional information to the classical prognostic parameters.