A proposal for a new histological classification scheme for predicting short-term tumor recurrence and death in patients with invasive ductal carcinoma of the breast.

Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.     

A Proposal for a New Histological Classification Scheme for Predicting Short-term Tumor Recurrence and Death in Patients with Invasive Ductal Carcinoma of the Breast

Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.     

Tumor cells in lymph vessels and lymph nodes closely associated with nodal metastasis by invasive ductal carcinoma of the breast

No studies have ever precisely investigated the mechanism of nodal metastasis based on the histological characteristics of tumor cells in lymph vessels and lymph nodes. The purpose of this study was to investigate whether the histological characteristics of tumor cells in lymph vessels and lymph nodes of 393 patients with invasive ductal carcinoma (IDC) were significantly associated with increased nodal metastasis compared with well known histological characteristics of their primary-invasive tumor cells. Multivariate analyses showed that having a single nodal metastasis was closely dependent on primary-invasive tumor size or distance of lymph vessel tumor emboli from the margin of the primary-invasive tumor ( P <0.05) and that having 2 or more nodal metastases was significantly associated with the histological characteristics of the nodal metastatic tumors independently of the size of the primary-invasive tumor, and the number of nodes with extra-nodal invasion (ENI) significantly increased the relative risk (RR) of 4 or more nodal metastases in IDCs ≤20 mm and >20 to ≤50 mm in size ( P <0.05). In IDCs >50 mm in size, number of lymph vessels invaded, severe fibrosis of the stroma of extra nodal invasive tumors, and distance of ENI from the node significantly increased the RR of 10 or more nodal metastases in the multivariate analysis ( P <0.05). The results of this study strongly suggest that the histological characteristics of tumor cells in lymph nodes and lymph vessels play an important role in nodal metastasis in IDCs of the breast.     

Histological factors for accurately predicting first locoregional recurrence of invasive ductal carcinoma of the breast

The accurate assessment of the risk of first locoregional recurrence is very important for improving the survival of patients with invasive ductal carcinoma of the breast. The present study investigated which histological factors (both well‐known histological factors and factors that we have proposed) were the most capable of accurately predicting first locoregional recurrence among 1042 patients with invasive ductal carcinoma and various tumor statuses (overall, nodal status, Union Internationale Contre le Cancer pathological TNM stage, adjuvant therapy status, and adjuvant radiotherapy status) using multivariate analyses by the Cox proportional hazard regression model. The present study clearly demonstrated that the best factor for accurately predicting locoregional recurrence was grade 3 lymph vessel tumor embolus (>4 mitotic figures and >6 apoptotic figures in tumor embolus), followed by type 2 invasive ductal carcinoma (negative for fibrotic foci but positive for atypical tumor‐stromal fibroblast), grade 2 lymph vessel tumor embolus (1–4 mitotic figures and >0 apoptotic figures in tumor embolus; >0 mitotic figures and 1–6 apoptotic figures in tumor embolus), primary invasive tumor cell‐related factors (>19 mitotic figures, presence of tumor necrosis, presence of skin invasion) and >5 mitotic figures in metastatic carcinomas to the lymph node. Our proposed factors were superior to well‐known histological factors of primary invasive tumors or clinicopathological factors for the accurate prediction of first locoregional recurrence in patients with invasive ductal carcinoma of the breast.     

Is invasive lobular carcinoma different from invasive ductal carcinoma?

AIMS: The purpose of this study is to determine whether the histopathologic features and outcome in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are different, and whether the histologic type is a prognostic factor for outcome. METHODS: A retrospective cohort study was conducted in consecutive 510 stage I/II breast carcinoma patients who underwent modified radical mastectomy. The features of 65 patients with ILC were compared with those of 445 patients with IDC. In patients with median follow-up period of 44 months, univariate and multivariate prognostic factor analyses for cancer-specific death and relapse were carried out. RESULTS: The median ages in patients with ILC and those with IDC were 52 and 41 (P=0.04). Tumor size, estrogen receptor positive expression and nodal positivity were not significantly different between the histologic types. Patients with ILC had more frequently (81.5%) low grade tumors and less lymphatic vascular invasion (9.3%) in primary tumor than those with IDC (P<0.05). Whereas the rates of 5-year overall survival were 94% in ILC and 90% in IDC, the rates of 5-year event-free survival were 71 and 67%, respectively (P=NS). Multivariate analyses in all patients demonstrated that tumor size, pathologic lymph node status and age at diagnosis were the most important prognostic factors for overall and event-free survival. Histologic type was not statistically significant for both outcomes. CONCLUSIONS: Although patients with ILC had older age, low grade tumor and less lymphatic vascular invasion, they had no survival advantage comparing with their counterparts. Histologic type was not an independent prognostic factor for outcome.     

Significance of nodal metastatic tumor characteristics in nodal metastasis and prognosis of patients with invasive ductal carcinoma of the breast

There is no study evaluating the significance of nodal metastatic tumor characteristics in tumor progression of invasive ductal carcinomas (IDCs) of the breast. The purpose of this study was to investigate whether nodal metastatic tumor characteristics play an important role in the tumor progression of IDCs. The subjects of this study were 205 IDC patients with nodal metastases. Significant associations with increased numbers of nodal metastases, and patient outcomes were evaluated by multivariate analyses, in comparison with well-known histological parameters. The numbers of lymph nodes with extra-nodal invasion and with extra-nodal blood vessel tumor emboli, the distance of extra-nodal blood vessel tumor emboli from the nodes, and the nodal tumor dimensions significantly increased the number of nodal metastases in the multivariate analysis ( P <0.001). Cox multivariate analyses showed that the parameters which significantly increased hazard rates (HRs) of disease-free survival (DFS), distant organ metastasis (DOM) and overall survival were 6 or more mi-totic figures of nodal metastatic tumors ( P <0.05). Six or more lymph nodes with extra-nodal invasion, and an extra-nodal blood vessel tumor emboli dimension of >0.6 mm significantly increased the HRs of DFS and DOM in multivariate analyses ( P <0.05). The present study demonstrated the important roles of nodal metastatic tumors in the tumor progression of IDCs. (Cancer Sci 2003; 94: 181–187)     

Fibrotic Focus in Invasive Ductal Carcinoma of the Breast: A Histopathological Prognostic Parameter for Tumor Recurrence and Tumor Death within Three Years after the Initial Operation

We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c- erb B-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1–3 and >3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR= 6.9, P<0.05 and RR=25.0, P< 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher HRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR=2.0, P < 0.001 and RR=5.9, P< 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.     

New prognostic factors associated with long-term survival in node-negative breast cancer patients

Background  This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Patients and Methods  Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). Results  Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. Conclusion  PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.     

Prognostic factors in soft tissue sarcomas. A multivariate analysis of 109 cases

Prognostic factors were evaluated in 109 soft tissue sarcomas of the extremities, walls of the trunk, head, and neck. All lesions were graded according to the systems proposed by the National Cancer Institute (NCI) and the French Federation of Cancer Centers (FNCLCC), and a correlation was found between tumor grade and prognosis. Univariate analysis selected the following variables as unfavorable prognostic factors: invasive tumor margins, extra-compartmental status, deep tumors, tumor diameters over 5 cm, inadequate excision, presence of necrosis, high mitotic count, histologically undifferentiated tumors, and blood vessel invasion. These variables were found to be interdependent. Multivariate analysis selected quality of surgery as the most important variable for predicting local recurrences. The factors selected with regard to overall and metastasis-free survival were tumor size, tumor margins, necrosis, and adequacy of excision. These results permitted classification of patients into four prognostic groups: two with good and two with bad prognosis. Five-year survival for the four groups was 100%, 83%, 53%, and 0%; 5-year metastatic rates were 0%, 12%, 67%, and 100%. Similar groups were obtained when the variables of tumor margins and size were combined with an adaptation of the NCI grading (low-grade tumors/high-grade tumors without necrosis/high-grade tumors with necrosis). Comparative analysis showed that patients with tumors of the same histologic grade or type were not necessarily classed in the same prognostic groups. A better clinicopathologic correlation was obtained using a combination of prognostic factors than with histologic grading or typing alone.     

Histological characteristics of tumors in blood vessels play an important role in tumor progression of invasive ductal carcinoma of the breast

Whether the characteristics of tumor cells in blood vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast is not known. The purpose of this study was to investigate the significance of the characteristics of tumor cells in blood vessels in relation to tumor progression in 247 IDC patients with blood vessel invasion, in comparison with well-known histological parameters. Blood vessel tumor embolus dimensions were measured. Nuclear atypia, numbers of mitotic and apoptotic figures, and fibrosis grade of tumor cells in blood vessels were assessed. Cox proportional hazard multivariate analyses showed that >2 mitotic figures in blood vessel tumors significantly increased the hazard rates (HRs) of disease-free survival ( P =0.002) and initial distant organ metastasis-free survival (IDOMS) in node-negative IDCs ( P =0.005), and the HRs of diseasefree survival (DFS, P =0.007) and IDOMS ( P =0.015) in node-positive IDCs. Apoptotic figures >2 in blood vessel tumor emboli significantly increased the HR of overall survival ( P =0.007) in node-positive IDCs. The present study showed the number of mitotic and apoptotic figures in tumor cells in the blood vessels to play a very important role in the tumor progression of IDCs. (Cancer Sci 2003; 94: 158–165)     

Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis

Aim/Background. MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis. Methods. Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically. Results. The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival. Conclusion. The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.     

D2-40与乳腺浸润性导管癌临床病理分析

目的:观察淋巴管密度与乳腺非特殊类型浸润性导管癌(IDC,NOS)临床病理关系。方法:用淋巴管内皮细胞抗体D2-40单克隆抗体标记70例乳腺IDC(NOS)淋巴管表达,计算淋巴管密度,并同时进行ER、PR、HER-2、p53、VEGF和CD44V6检测,分析LVD与各临床病理指标的关系。结果:在IDC(NOS)中,D2-40标记的LVD与临床分期和腋淋巴结转移有关(P<0.05),而与年龄、组织学分级、及肿瘤直径无关(P>0.05)。进一步对临床分期行L-S-D检验,发现临床分期I期中的LVD与临床分期II、III期中的LVD有显著性差异,而临床分期II、III期间的LVD并无显著性差异。在IDC(NOS)中,D2-40标记的LVD与CD44V6表达相关(P<0.05),与ER、PR、HER-2、p53及VEGF的表达无关(P>0.05)。多因素分析显示,在IDC(NOS)中,D2-40标记的LVD与腋淋巴结转移和CD44V6有关(P<0.05),而与年龄、组织学分级、肿瘤直径、临床分期、ER、PR、HER-2、p53及VEGF无关(P>0.05)。结论:在IDC(NOS)中,D2-40标记的LVD与淋巴结状态相关,提示LVD可能与乳腺癌的预后有关,可能成为乳腺癌预后的独立指标。在IDC(NOS)中,D2-40标记的LVD与CD44V6表达呈正相关,并具有统计学意义,提示在肿瘤的生长过程中,CD44V6可能通过裂解细胞间质,促进肿瘤生长,导致间质中淋巴管密度增加,提高了肿瘤转移的机率。     

Determining of metastatic lymph node ratio in patients who underwent D2 dissection for gastric cancer

The purpose of this study was to determine outcome of the ratio of metastatic lymph nodes to the total number of dissected lymph nodes (MLR) in patients with gastric cancer. We retrospectively analyzed 111 patients who underwent D₂ lymph node dissection. The prognostic factors including UICC/AJCC TNM classification and MLR were evaluated by univariate and multivariate analysis. The MLR was significantly higher in patients with a larger tumor, lymphatic vessel invasion, blood vessel invasion and perineural invasion, and advanced stage. Moreover, the MLR was significantly associated with the depth of invasion and the number of lymph node metastasis. The univariate analysis revealed for overall survival (OS) that stage of disease, lymphatic vessel invasion, blood vessel invasion, perineural invasion, lymph node metastasis (UICC/AJCC pN stage) and MLR were relevant prognostic indicators. Furthermore, both UICC/AJCC pN stage and MLR were detected as prognostic factor by multivariate analysis, as was perineural invasion. Our results indicated that MLR and UICC/AJCC pN staging system were important prognostic factors for OS of patients with D₂ lymph node dissection in gastric cancer in a multivariate analysis. MLR may be useful for evaluating the status of lymph node metastasis in gastric cancer.     

Comparison of the Characteristics of Medullary Breast Carcinoma and Invasive Ductal Carcinoma

Purpose

Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC.

Methods

We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010.

Results

Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692).

Conclusion

Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.     

三阴性乳腺癌的临床病理特点及预后分析研究

目的:探讨三阴性乳腺癌患者临床病理特点、生存率以及影响预后的因素。方法:回顾性分析30例三阴性乳腺癌患者的资料,分析其临床病理特点、免疫组化指标和各种治疗方式对生存率的影响。结果:全组30例患者均为女性,占同期收治乳腺癌患者的5.7%,中位年龄50岁(39-76岁)。其中,浸润性导管癌21例(70.0%),单纯癌4例(13.3%),髓样癌2例(6.7%),管状腺癌2例(6.7%),导管内癌1例(3.3%)。Ⅰ期患者5例(16.7%),Ⅱ期15例(50.0%),Ⅲ期8例(26.7%),Ⅳ期2例(6.7%)。核分级1级4例(13.3%),2级11例(36.7%),3级15例(50.0%)。伴有脉管瘤栓10例(33.3%),伴有神经浸润5例(16.7%)。中位生存时间3.8年(1.6-7.5年)。单因素分析结果显示,影响总生存的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润。多因素分析结果显示,肿瘤大小和淋巴结状态是影响预后的独立因素。3年总生存率65.7%。结论:三阴性乳腺癌发病率较低,组织学分级较高,多为浸润性导管癌,易较早出现复发和转移。影响生存率的因素为肿瘤大小、淋巴结状态、临床分期、脉管瘤栓和神经浸润,其中影响预后的独立因素是肿瘤大小和淋巴结状态。     

Pathological factors related to lymph node metastasis of submucosally invasive gastric cancer: criteria for additional gastrectomy after endoscopic resection

Background

There are currently no universally accepted indications and criteria for additional gastrectomy after endoscopic resection of submucosally invasive cancer. The purpose of the present study was to establish accurate indications and criteria for such additional gastrectomy on the basis of lymph node metastasis risk.

Methods

We investigated 130 submucosally invasive gastric cancers and analyzed the pathological risk factors for lymph node metastasis. The tumors were evaluated for pathological factors in the area of invasion, and factors were compared between the cases with lymph node metastasis and those without.

Results

Univariate logistic regression analysis showed that tumor minor axis length, depth of invasion, histological classification of the area of submucosal invasion, absence of lymphoid infiltration, ulceration or scar in the lesion, and lymphatic and venous invasion are statistically significant risk factors for lymph node metastasis. Multivariate logistic regression analysis showed that the absence of lymphoid infiltration and the presence of lymphatic invasion are statistically significant as risk factors for lymph node metastasis.

Conclusions

We present a scoring system on the basis of the pathological criteria tested in this study. Our findings enable more accurate identification of patients who should undergo additional gastrectomy after endoscopic resection.     

Primary tumour-vessel tumour-nodal tumour classification for patients with invasive ductal carcinoma of the breast

There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour-vessel tumour-nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.     

Clinicopathological evaluation of patients surviving stomach cancer for 10 years following gastrectomy

The clinicopathological findings on 232 patients with advanced gastric cancer who survived longer than 10 years after curative surgery were reviews and compared with those on 287 patients who died within 5 years of their operation. There were significantly more 10-year survivors in the group whose tumor size was less than 5 cm, where the center was not located in the cardia, in patients without lymph node involvement, less vessel invasion and higher lymphocyte infiltration around the stroma of the cancerous nests. No statistical differences were observed with regard to patient age, sex, Borrmann classification, histological types and invasive patterns between 10-year survivors and patients who died less than 50 years postoperatively.     

Impact of tumor‐associated macrophages on invasive ductal carcinoma of the pancreas head

Tumor‐associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumor‐associated macrophages can be affected by cancer‐related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM‐related factors and the clinical impact of TAMs. CD68 (a pan‐macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease‐free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02411.x, 2012)