Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Tumor labeling indices of primary breast cancers and their regional lymph node metastases

BACKGROUND: Tumor labeling index has emerged as a strong predictor of the clinical course of women with breast cancer. This study investigated whether labeling index of primary tumors correlates with labeling indices of concurrent regional node metastases. METHODS: With appropriate written consent, preoperative in vivo infusion of the thymidine analogue 5-bromodeoxyuridine (BrdUrd) was used to label 109 human breast cancers. Labeled S-phase cells were identified immunohistochemically with an antibody specific to DNA-incorporated BrdUrd. Labeling index was the fraction of labeled nuclei in 2000 tumor nuclei. For 30 women, there was sufficient cancer in axillary lymph nodes to compare labeling indices in primary breast cancer and regional lymph node metastases. RESULTS: The 30 women were from 25 to 82 years of age. Tumors were from 1 to 12 cm in size and there were from 1 to 26 positive nodes. Tumor labeling index ranged from 0.1% to 34%, (mean, 11.1%; median, 10.3%) and axillary lymph node metastasis labeling index ranged from 0.1% to 27.7% (mean, 10.8%; median, 10.0%). There was strong correlation between primary tumor labeling index and regional lymph node metastases labeling index (r = 0.82, with 95% confidence interval 0.65-0.91). The correlation persisted within subgroups according to age, tumor size, number of positive nodes, and hormone receptor status. Primary tumor and lymph node metastases labeling indices also had statistically similar relationships with age, level of hormone receptors, tumor size, and number of positive nodes. CONCLUSIONS: Primary tumor and regional node labeling indices correlate strongly; the relationship is not influenced by age, level of hormone receptors, tumor size, or number of positive nodes.     

Serous cystadenoma of the pancreas with hypoplasia of the dorsal pancreas: report of a case

Transforming growth factor-betas (TGFbetas) play a prominent role in tumour growth and metastasis by enhancing angiogenesis and suppressing immune surveillance. Despite the increased interest in the effect of TGFbetas on tumour progression, little is known about the importance of TGFbeta3 and its receptor CD105 in breast cancer. In the present study, we measured the plasma levels of TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of the 80 patients, 14 were histologically confirmed as having axillary lymph node metastases, while the remainder had no evidence of lymph node involvement. The results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were significantly elevated in patients with positive lymph nodes compared to those without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105-TGFbeta3 complex correlated with lymph node status. The only patient who died of the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex and positive lymph nodes; this patient developed lung metastases within 2 years of diagnosis. No significant correlation was seen between either TGFbeta3 or CD105-TGFbeta3 complex levels and tumour stage, size or histological grade. Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage, grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3 complex may be of prognostic value in the early detection of metastasis of breast cancer.     

Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma

BACKGROUND AND OBJECTIVE: The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. METHODS: From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. RESULTS: The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). CONCLUSIONS: If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.     

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.     

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.     

Para-aortic lymph node metastasis in carcinoma of the distal bile duct

BACKGROUND/AIMS: Lymph node dissection plays an important role in radical surgery for pancreaticoduodenal carcinomas. The aim of this study was to identify the critical areas of lymph node dissection in carcinoma of the distal bile duct. METHODOLOGY: Between January 1995 and December 1996, 20 consecutive patients with distal bile duct cancer underwent pancreaticoduodenectomy with extended lymph node dissection (including the para-aortic nodes). Histopathologic findings were examined with special reference to lymph node metastasis. RESULTS: Histological evidence of lymph node metastasis was found in 11 patients (55%). The areas with frequent metastases were the posterior pancreaticoduodenal lymph nodes (35%), and the nodes around the hepatoduodenal ligament (35%) and around the common hepatic artery (30%). Para-aortic lymph node involvement was identified in 5 patients (25%). Most of these existed in the inter-aorticocaval space. Pancreatic parenchymal invasion was present in 10 patients. Half of the patients with pancreatic invasion had para-aortic nodal involvement. Para-aortic lymph node metastasis was significantly associated with pancreatic parenchymal invasion (p<0.05). CONCLUSIONS: In carcinoma of the distal bile duct with pancreatic parenchymal invasion, extended lymph node dissection (including para-aortic nodes) should be undertaken because of the relatively high incidence of metastasis.     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.     

Axillary lymph node metastases of bronchogenic carcinoma

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.     

T1a and T1b breast cancer: a twelve-year experience

To understand the prevalence of axillary node metastasis and survival of patients with T1a and T1b breast cancers, we reviewed the experience at a large community hospital. All patients in the William Beaumont Hospital tumor registry with breast cancer treated between January 1983 and November 1995 were evaluated for tumor size, age, cell type, and the presence or absence of axillary node disease. Long-term survival was evaluated in patients treated between 1983 and 1992. The patients were defined as premenopausal or postmenopausal based on age (49 years or less, premenopausal; 50 years or greater, postmenopausal). Of the 4590 patients treated for breast cancer from 1983 to 1995, 915 had tumors 1.0 cm or less in size. Of 181 patients who had T1a cancer, 27 were premenopausal, and 154 were postmenopausal. Twenty-three premenopausal patients had axillary lymph nodes examined, two (8.7%) had histologically positive lymph nodes. Of 118 postmenopausal patients who had axillary nodes examined, six (5.1%) had positive lymph nodes. In those with T1b tumors, 130 patients were premenopausal; 604 patients were postmenopausal. Of these, 119 premenopausal patients had axillary nodes examined, and 29 (24.4%) had positive lymph nodes. Of 464 postmenopausal patients who had axillary nodes examined, 66 (14.2%) had positive nodes. The overall, disease-free, and tumor-specific survival rates for patients with T1a tumors were 93.8, 87.5, and 93.8 per cent (premenopausal) and 86.2, 95.4, and 95.4 per cent (postmenopausal), respectively. These survival rates for patients with T1b tumors were 87.8, 87.8, and 91.1 per cent (premenopausal) and 82.9, 88.5, and 92.9 per cent (postmenopausal), respectively. Premenopausal T1b patients had a higher rate of nodal involvement than postmenopausal T1b patients (P = 0.011). Postmenopausal T1b patients had a higher nodal metastasis rate than postmenopausal T1a patients (P = 0.01). T1b patients had a higher rate of axillary involvement than did T1a patients (P = 0.0018). Based on the rate of axillary lymph node metastasis and survival statistics, there may be a role for axillary node dissection in select patients with tumors less than 1.0 cm. in size.     

Expression of CD44 variant 6 and lymphatic invasion: importance to lymph node metastasis in gastric cancer

Lymph node metastasis is a critical prognostic factor for gastric cancer. In the present investigation we examined clinicopathologic factors influencing the metastatic processes to the lymph mode and their prognostic importance. A randomly selected group of 98 patients with adenocarcinomas of the stomach who underwent gastrectomy plus systematic lymph node dissection at Osaka Police Hospital from 1991 to 1996 were analyzed. Altogether 37 (38%) cancers were positive for CD44 variant 6 (v6) staining, 31 (32%) were intermediately stained, and 30 (30%) were negative. CD44-v6 expression correlated well with lymph node metastasis. Expression of CD44-v6 and lymphatic invasion were independent risk factors for metastatic lymph nodes. Among the patients with CD44-v6-positive and lymphatic invasion-positive cancers, 88% had lymph node metastasis, whereas only 13% of patients negative for both factors had lymph node metastasis. Although CD44-v6 expression and lymphatic invasion have been reported to be risk factors for recurrence and a poor prognosis, in this investigation these factors were found not to be significant for hematogenous and lymphatic recurrences or overall survival rates. Thus expression of CD44-v6 and lymphatic invasion may regulate lymph node metastases from gastric cancer.     

Influence of vegetative cycle of asparagus (Asparagus officinalis L.) on copper, iron, zinc and manganese content

A case is reported of a 51-year-old woman who had a hysterectomy and bilateral salpingo-oophorectomy in the same year, following a radical mastoidectomy for breast cancer with metastases to the axillary lymph nodes. Histological examination showed breast cancer metastatic to uterine leiomyoma. The literature about metastasis of extragenital cancer to a leiomyoma is reviewed, and the possible mechanism involved is discussed.     

Prognostic factors in oligodendrogliomas

Among 601 patients with early gastric cancer (EGC), the clinicopathological findings of 5 patients (invasion of the mucosal layer in 2 and of the submucosal layer in 3) with distant lymph node metastasis according to TNM classification (third- or fourth-tier lymph node metastasis according to the Japanese classification) were investigated. The proliferating-cell nuclear antigen (PCNA) expression of EGC was also examined immunohistologically. The sites of distant metastasis were the nodes at the root of the mesentery, in the hepatoduodenal ligament, and the paraaortic nodes. While the PCNA-positive rate of EGC with distant lymph node metastasis (35.4%) was significantly higher than that of EGC without lymph node metastasis (14.7% P = 0.01), it was similar to that of EGC with perigastric lymph node metastasis. The cumulative survival rate of the EGC patients with distant lymph node metastasis (5-year survival rate 20.0%) was significantly lower than that without lymph node metastasis (88.2%, P < 0.0001), first-tier lymph node metastasis (76.9%, P < 0.04), or second-tier lymph node metastasis (77.1%, P < 0.04). Thus, although the prognosis of EGC patients with distant lymph node metastasis was poor, a dissection of the distant lymph nodes should be performed when metastasis is suspected.     

Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer

BACKGROUND: Whether any difference exists in clinical characteristics between resected non-small cell lung cancer with either skip or ordinary mediastinal lymph node metastases (N2 disease) needs to be clarified. METHODS: There were 110 patients with stage IIIA N2 disease. Thirty-three patients demonstrating no metastasis at the hilar nodes [skip (+) group] were compared with the other 77 patients [skip (-) group]. To investigate the extent of nodal involvement, we classified the mediastinal lymph nodes into three regions (superior, inferior, or aortic). RESULTS: There were no significant differences regarding histologic type, T status, or the site of the primary tumors between the skip (+) and the skip (-) N2 groups. In the skip (+) group, mediastinal node metastasis was found in only one region (level 1) in 30 patients (90.9%) and in two regions (level 2) in 3 (9.1%), whereas 28 patients (36.4%) from the skip (-) group revealed mediastinal metastasis at two or three regions (level 2 or 3). The overall survival rate at 5 years after operation was 35% in the skip (+) group and 12.7% in the skip (-) group (p = 0.054). This favorable clinical outcome in the skip (+) group could be explained partially by the higher proportion of patients with level 1 metastases. Furthermore, regarding patients with level 1 disease, the skip (+) group tended to have a better prognosis than the skip (-) group (p = 0.096). CONCLUSIONS: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease.     

Lymphatogenous spread of renal cell carcinoma: an autopsy study

PURPOSE: We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS: From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.     

Lymph node revealing solution: a new method for detection of minute axillary lymph nodes in breast cancer specimens

The staging and prognosis of patients with breast cancer is related to the presence or absence of axillary lymph node involvement. However, in some cases no lymph nodes or too small a number of lymph nodes are revealed by the traditional method of palpating and sectioning the axillary fat. In the present study we demonstrate the usefulness of the lymph node revealing solution (LNRS) in breast cancer. Specimens from 13 patients, in whom <10 lymph nodes were identified in the axilla by the traditional method, were included in the study. After excising the lymph nodes by the traditional method, axillary tissue was immersed in LNRS for 6-12 hours. Additional lymph nodes, which stood out as white chalky nodules, were excised and processed as usual. The LNRS increased the mean number of nodes per case from 6.0+/-2.5 found by the traditional method to 12.54+/-4.61 nodes per case (p < 0.01). The size of the nodes identified by the LNRS was significantly smaller (p < 0.01) than those detected by the traditional method. The LNRS changed the lymph node stage of the disease in four of the studied cases (30%). LNRS seems to be the technique of choice for detection of axillary lymph nodes in cases where the number of detected lymph nodes by the traditional method is too small for accurate staging.     

Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival

BACKGROUND AND OBJECTIVES: Decreased expression of the E-cadherin/alpha-catenin cell-cell adhesion complex is considered to elicit detachment of tumor cells from primary lesions and development of metastases. The immunohistochemical profile of alpha-catenin in colorectal cancer, as well as its correlation with differentiation, lymph node/liver metastasis and patient survival is presented in this study. METHODS: Alpha-Catenin expression was investigated with immunohistochemistry technique, in 85 paraffin-embedded and 21 fresh frozen specimens, including 82 colon adenocarcinomas, 10 adenomas, 10 lymph nodes, and 3 liver metastases. Preserved alpha-catenin expression was considered for those tumors that demonstrated more than 90% alpha-catenin(+) cancer cells and reduced alpha-catenin expression for those tumors with less than 90% alpha-catenin(+) cancer cells. The chi2-test was used to calculate the statistical correlation of alpha-catenin expression with grade of differentiation and metastatic potential and the log-rank test for the correlation with survival rate. RESULTS: Normal mucosa, as well as 8/10 of the colon adenomas, showed strong membranous alpha-catenin expression. Reduced alpha-catenin expression was found in 32/82 (39%) colorectal cancers examined, which was associated with de-differentiation (P < 0.01), lymph node metastasis (P < 0.025), and poor clinical outcome (P < 0.012). Alpha-Catenin expression was preserved in 3 liver metastases and their corresponding primary tumors. By contrast, 6/10 of lymphogenous metastases showed decreased alpha-catenin expression. CONCLUSIONS: Our findings demonstrate a significant down-regulation of alpha-catenin expression in colorectal cancer which is associated with poor differentiation, higher metastatic potential and unfavorable prognosis. These preliminary results suggest that alpha-catenin may be a useful marker of invasiveness, metastatic potential, and survival in colorectal cancer patients.