Invasive lobular carcinoma of the breast with colonic metastasis: a case series of three patients.

BACKGROUND: Although metastatic spread of breast cancer to the gastrointestinal tract is very rare, it is more likely to occur in invasive lobular carcinoma (ILC) than in ductal carcinoma. Colonic metastasis is particularly rare, and the treatment strategies for these cases are not clearly defined. Herein, we report three cases of ILC with various abdominal symptoms associated with colonic metastasis. CASE PRESENTATION: Case 1 A 70-year-old female patient with vomiting and melena was referred to our hospital. Endoscopic examination revealed a Dieulafoy ulcer in the rectum and an elevated lesion in the descending colon. She also had two breast nodules, and was diagnosed as ILC with colonic metastasis. Considering her general condition, the best supportive care (BSC) was offered. The patient died 4 months after confirmation of the diagnosis. Case 2 An 80-year-old female patient presented with diarrhea and vomiting. She was diagnosed with ILC with colonic metastasis, and a coloscopy revealed stenosis of the transverse colon with a metastatic lesion. Ileosigmoid bypass surgery was performed for intestinal obstruction, and systemic treatment for breast cancer was initiated. The patient developed peritoneal carcinomatosis and died 1 year and 2 months after surgery. Case 3 A 56-year-old female patient underwent left total mastectomy for ILC, and laparoscopic transverse colectomy was conducted for a colonic lesion 9 years and 2 months after. The diagnosis as colonic metastasis was not confirmed at that time. Two years and 2 months later, torose lesions were detected in the hepatic flexural and descending colon, and histopathological findings indicated that all colon tumors, including the previously resected tumor, were metastatic spread of ILC. Systemic treatment was continued, but the transverse colonic lesion penetrated the abdominal wall, and an abscess formed 2 years and 11 months after the resection. The fistula improved by continuous suction drainage following ileostomy but recurred, and the patient died 3 years and 8 months after colectomy. CONCLUSIONS: Colonic metastases from breast cancer can trigger various abdominal symptoms, and the prognosis in these cases is generally poor. In selected cases, surgical treatment for abdominal symptoms and subsequent systemic therapy can contribute to a prolonged prognosis.

Hepatocellular carcinoma with regional lymphadenopathy caused by sarcoid-like reaction: a case report.

BACKGROUND: Sarcoid-like reaction (SLR) is a histological pattern of granulomatous inflammation that is clinically differentiated from sarcoidosis. Since SLR is known to occur in several neoplasias and occasionally causes lymphadenopathy and mimics metastatic malignancy, it needs to be considered whether lymphadenopathy is due to metastasis or SLR for the choice of cancer treatment. Few cases of hepatocellular carcinoma (HCC) with SLR have been reported. Here, a case of HCC with lymphadenopathy diagnosed as SLR without metastasis is presented. CASE PRESENTATION: A 69-year-old woman was admitted to our hospital because of upper abdominal pain. She tested positive for hepatitis C virus ribonucleic acid. Imaging modalities showed an 81 × 65-mm-sized tumor with multiple nodules in segment 3 and a 17 × 12-mm-sized tumor in segment 5 with a common HCC enhancement pattern. In addition, a lymph node in the hepatoduodenal ligament was enlarged at 13 mm in size, suggesting the metastasis of HCC. Hepatectomy of the lateral segment and segment 5 and lymph node dissection in the hepatoduodenal ligament were performed. Both tumors in segments 3 and 5 were pathologically diagnosed as HCC without vessel invasion. The tumors contained necrotic cells and epithelioid cell granulomas with multinucleated giant cells, which is typically observed in sarcoidosis. The dissected lymph nodes also contained epithelioid cell granulomas, as well as giant cells with asteroid bodies. There was no malignancy in the lymph nodes. The pathological findings suggested the coexistence of malignancy and sarcoidosis. However, since the patient did not show any typical findings of pulmonary or cardiac sarcoidosis, the case was diagnosed as HCC with SLR in the primary lesion and regional lymph nodes. CONCLUSIONS: SLR needs to be considered in the differential diagnosis when a cancer patient develops lymphadenopathy. However, lymphadenopathy due to SLR is indistinguishable from that due to metastasis even when using multiple imaging modalities. Pathological examinations may be helpful for the diagnosis.

Adenocarcinoma arising from an ectopic pancreas in the duodenum: a case report.

BACKGROUND: The malignant transformation of an ectopic pancreas in the duodenum is extremely rare. Herein, we report a case of an adenocarcinoma that arose from an ectopic pancreas. We also reviewed 14 cases of malignant transformations arising from an ectopic pancreas in the duodenum that were previously published. CASE PRESENTATION: An 81-year-old man with a 1-month history of vomiting was admitted to our institution. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) scans revealed an obstruction at the first part of the duodenum. A distal gastrectomy was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed adenocarcinoma that arose from an ectopic pancreas (Heinrich type 1). The patient is alive without relapse at 18 months of follow-up. CONCLUSIONS: Adenocarcinoma that arises from an ectopic pancreas should be considered when an obstruction is identified in the duodenum.

A left lung abscess with a displaced subsegmental bronchus and anomalous pulmonary artery and vein: a case report.

BACKGROUND: Since a displaced bronchus related to the left upper lobe is an uncommon anatomical anomaly, it has a risk of being accidentally resected during left upper lobe resection unless they are identified preoperatively. A case of video-assisted thoracic surgery (VATS) segmentectomy that was safely performed under preoperative identification of a displaced subsegmental bronchus and anomalous pulmonary vessels is presented. CASE PRESENTATION: A 48-year-old woman visited our hospital because of an abnormal shadow on a radiograph on a health check. The chest computed tomography (CT) showed a multicystic mass with a diameter of 35 mm on dorsal interlobar parenchyma between the S1+2 and S6 segments in the left lung. The three-dimensional (3D) CT with multiplanar reconstruction showed that B1+2b+c passed to the dorsal side of the left main pulmonary artery (PA), which was considered a displaced bronchus. The branch of A6 arose from the left main PA at the level of the branches of A3 and A1+2, more proximal than the normal anatomy, and passed to the dorsal side of a displaced B1+2b+c. The branch of V1+2 passed between B6 and the bronchus to the basal segment and joined V6 at the dorsal side of the pulmonary hilum. Intraoperative findings of the anatomy of the bronchi and pulmonary vessels were exactly the same as the preoperative 3D CT findings, so segmentectomy of S1+2b+c and S6 by VATS was performed safely. Then there were accessory fissures between S1+2 and S3 and between S6 and the basal segment. The pathological diagnosis was a left lung abscess. CONCLUSIONS: A preoperative 3D CT may be helpful for identifying anatomical anomalies. An anatomical anomaly should be suspected if accessory fissure is found during surgery.

Cervical Castleman's disease mimicking lymph node metastasis of esophageal carcinoma.

Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder of unknown etiology. A rare case of cervical CD diagnosed at lymph node dissection for esophageal carcinoma is reported. An esophageal tumor was identified in a 67-year-old man during a follow-up examination after surgery for oral carcinoma. Esophagoscopy revealed a type 1 tumor in the cervical esophagus. Histology of esophagoscopic biopsies indicated squamous cell carcinoma. Contrast-enhanced computed tomography revealed swollen lymph nodes of the right cervical region. No distant metastasis was detected. Esophageal carcinoma, T2N2M0, Stage IIIA was diagnosed. Neoadjuvant chemotherapy was recommended, but the patient rejected the chemotherapy. The patient underwent laparoscopic-assisted transhiatal esophagectomy. The histopathological diagnosis was moderately differentiated squamous cell carcinoma with pT1bN0M0, Stage IA. On histology, the swollen lymph nodes of the right cervical region revealed CD. The patient's postoperative course was relatively good.

Pancreatic Pseudocyst Ruptured due to Acute Intracystic Hemorrhage.

Rupture of pancreatic pseudocyst is one of the rare complications and usually results in high mortality. The present case was a rupture of pancreatic pseudocyst that could be treated by surgical intervention. A 74-year-old man developed abdominal pain, vomiting, and diarrhea, and he was diagnosed with cholecystitis and pneumonia. Three days later, acute pancreatitis occurred and computed tomography (CT) showed slight hemorrhage in the cyst of the pancreatic tail. After another 10 days, CT showed pancreatic cyst ruptured due to intracystic hemorrhage. Endoscopic retrograde cholangiopancreatography revealed leakage of contrast agent from pancreatic tail cyst to enclosed abdominal cavity. His left hypochondrial pain was increasing, and CT showed rupture of the cyst of the pancreatic tail into the peritoneal cavity was increased in 10 days. CT showed also two left renal tumors. Therefore we performed distal pancreatectomy with concomitant resection of transverse colon and left kidney. We histopathologically diagnosed pancreatic pseudocyst ruptured due to intracystic hemorrhage and renal cell carcinoma. Despite postoperative paralytic ileus and fluid collection at pancreatic stump, they improved by conservative management and he could be discharged on postoperative day 29. He has achieved relapse-free survival for 6 months postoperatively. The mortality of pancreatic pseudocyst rupture is very high if some effective medical interventions cannot be performed. It should be necessary to plan appropriate treatment strategy depending on each patient.

Giant primary angiosarcoma of the small intestine showing severe sepsis.

Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40 °C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm × 17.5 cm × 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

Pancreatic arteriovenous malformation.

An unusual case of pancreatic arteriovenous malformation (P-AVM) combined with esophageal cancer is reported. A 59-year-old man was admitted with upper abdominal pain. Contrast-enhanced computed tomography showed numerous strongly enhanced abnormal vessels and a hypovascular lesion in the area of the pancreatic tail. Angiographic study of the celiac artery confirmed racemose vascular networks in the tail of the pancreas. Endoscopic retrograde pancreatography revealed narrowing and displacement of the main pancreatic duct in the tail of the pancreas. Screening esophagoscopy showed a 0-IIa+IIc type tumor in the lower thoracic esophagus. Histological examination of esophagoscopic biopsies showed squamous cell carcinoma. Based on these findings, P-AVM or pancreatic cancer and esophageal cancer were diagnosed. Video-assisted thoracoscopic esophagectomy and distal pancreatectomy were performed. Histological examination of the resected pancreas revealed abundant abnormal vessels with intravascular thrombi. In addition, rupture of a dilated pancreatic duct with pancreatic stones and both severe atrophy and fibrosis of the pancreatic parenchyma were observed. The final diagnoses were P-AVM consequent to severe chronic pancreatitis and esophageal carcinoma. The patient's postoperative course was relatively good.

Lymphoepithelial cyst of the pancreas.

Cystic lesions of the pancreas can be divided into true cysts, pseudocysts, and cystic neoplasms. Lymphoepithelial cysts (LECs) are a type of true cyst that can mimic pseudocysts and cystic neoplasms. LECs are rare lesions; fewer than 90 cases have been reported in the English language literature. The case of a 60-year-old man with an LEC of the pancreas is reported. He was admitted with upper abdominal discomfort. Computed tomography showed a 64 × 39 mm cystic mass in the retroperitoneum behind the duodenum and inferior caval vein. Magnetic resonance imaging revealed a right-sided mass on T1-weighted imaging, with a clear boundary between the mass and its surroundings, except for the pancreas. The mass had an inhomogeneous intensity on T2-weighted imaging. Within the mass, small floating nodules with low intensity were seen. Endoscopic ultrasound showed many high-echoic nodules and smaller grains scattered everywhere in the mass. Fine needle aspiration and cytologic examination were performed. Characteristic chylaceous fluid was obtained in which anucleate squamous cells were found. There were also a few atypical large cells with irregularly shaped marked nucleoli and degenerative cytoplasm. Cytologic diagnosis was suspicious for malignancy. The lesion was diagnosed as a retroperitoneal cyst, probably of pancreatic origin. Since a neoplastic lesion could not be ruled out, surgery was performed. The lesion was palpable on the dorsal side of the second portion of the duodenum. The mass was completely resected. Macroscopically, the lesion was a multilocular cyst with a thin septal wall. The cyst was filled with cottage cheese-like substance. Microscopically, the cyst wall was composed of stratified squamous epithelium and dense subepithelial lymphatic tissue with developed lymph follicles. The epithelial cells had no atypia. The histopathologic diagnosis was LEC of the pancreas. The patient's postoperative course was good.

New invagination procedure for pancreaticojejunostomy using only four sutures.

BACKGROUND: Pancreaticoenterostomy remains one of the most stressful parts of pancreatoduodenectomy. We introduce herein a new convenient and secure invagination procedure for pancreaticojejunostomy. METHODS: We performed our new procedure during pancreatoduodenectomy in 15 consecutive patients (7 men, 8 women). The features of the procedure are as follows. First, it is performed using only four sutures. Second, the pancreas stump is invaginated into the jejunum, mainly by two sutures that penetrate the parenchyma and are continuously purse-string sutured to the jejunum. Third, all needle holes on the surface of the pancreas are covered with the jejunal wall. RESULTS: Eight patients were classified as showing no pancreatic fistula, and seven displayed a grade A fistula, according to the International Study Group on Pancreatic Fistula criteria. The median operating time for these 15 patients using the present procedure was about 60 min shorter than that for the previous nine patients who underwent duct-to-mucosa pancreaticogastrostomy in our hospital. CONCLUSIONS: The present method allows pancreaticojejunostomy to be performed swiftly and conveniently.

Inadvertent Ingestion of a Press-Through Package Causing Perforation of the Small Intestine within an Incisional Hernia and Panperitonitis.

A 90-year-old woman was admitted to the emergency department of our hospital with abdominal pain and a fever of up to 39°C. She had a history of hysterectomy about 30 years previously, and redness and swelling were seen at the abdominal median scar. Serum biochemistry showed minor elevation of C-reactive protein and creatine phosphokinase. Abdominal computed tomography (CT) showed an edematous intestinal tract image over the median abdominal wall. Incarcerated incisional hernia and intestinal necrosis were suspected. Therefore, emergency surgery was performed. On laparotomy, abundant purulent ascitic fluid was found. The small intestine was incarcerated about 100 cm orally from the terminal ileum, and a 2-mm perforation was present in the incarcerated small intestine. In addition, some white areas measuring 1 mm were found in the small intestinal wall. A press-through package (PTP) of a tablet was confirmed in the intestinal tract near the perforated area. We removed the PTP through the perforation and performed direct suture. Postoperatively, we retrospectively reviewed the CT image and found a high-density shadow which seemed to represent the PTP.

Long-term survival of resected advanced gastric cancer with hepatic and pancreatic invasion.

A 64-year-old man was transferred to our division with a suspicion of gastric cancer. Computed tomography showed widespread irregular thickening of the stomach walls close to the liver and pancreas. Gastrointestinal fiberscopy showed a type 5 tumor in the upper to lower stomach, histologically diagnosed as tubular adenocarcinoma. Gastric cancer with hepatic and pancreatic invasion was diagnosed. Distant metastasis was not proven and complete resection was planned. At laparotomy, the tumor showed general expanding growth and invasion through the lateral segment of the liver and pancreas. Total gastrectomy and combined resection of the distal pancreas, spleen and left segment of the liver were performed. Hepatic and pancreatic invasion and lymph node metastasis were microscopically proven. Pancreatic fistula occurred postoperatively. On postoperative days 40, he was discharged. He received two cycles of adjuvant tegafur/gimeracil/oteracil chemotherapy. He has had no sign of recurrence for 7 years and 8 months.

Intrapulmonary cellular schwannoma.

A 75-year-old asymptomatic woman was admitted to our hospital after an abnormal shadow was found on a chest roentgenogram. Chest computed tomography showed a round mass in the right lower lobe. Magnetic resonance imaging showed the mass with high signal intensity on T2-weighted images and intermediate signal intensity on T1-weighted images. Fluorine-18-fluorodeoxyglucose-positron emission tomography showed high fluorine-18-fluorodeoxyglucose accumulation in the mass. A lobectomy was performed thoracoscopically. The pathologic diagnosis was cellular schwannoma. Immunohistochemical staining demonstrated the presence of S-100 protein, and the Ki67 labeling index was 12%. We present this case of intrapulmonary cellular schwannoma, which is extremely rare.

Multiple endocrine neoplasia type 1-associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas.

A novel combination of tumors was found in a 68 year-old female with Multiple Endocrine Neoplasia type-1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense-cored neurosecretory granules, larger zymogen-like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.

Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis.

Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.

Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling.

BACKGROUND: We assessed the predictability of various classes of gastric carcinoma defined by clinicopathological parameters, such as invasiveness and clinical outcomes, using cDNA array data obtained from 54 cases. MATERIALS AND METHODS: We searched an optimal combination of genes to discriminate the classes defined with the clinicopathological parameters by using a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). With the selected features (gene set), we evaluated the predictability of each parameter in a leave-one-out cross-validation test. RESULTS: We successfully selected sets of genes for which the classifier predicted better versus worse overall survival (tumor-specific death) and tumor-free survival (recurrence), with respective classification rates of 94 and 92%. A contingency table analysis (chi2 test) and Cox proportional hazard model analysis revealed that lymph node metastasis is the most important factor (confounding factor) in patients' prognoses and risks of recurrence. The feature subset selection procedure successfully extracted expression patterns characteristic of lymph node metastasis and lymphatic vessel invasion, yielding 92 and 98% prediction accuracies for these respective factors. CONCLUSION: We conclude that expression profiling using feature subset selection provides a powerful means of stratification of gastric cancer patients in regard to the prognostic factors. Further studies should be warranted to apply this method to personalization of the treatment options.

Aberrant expression of HOX genes in human invasive breast carcinoma.

HOX genes are known not only as master genes that control the morphogenesis, but also as regulator genes that maintain tissue or organ specificity in the adult body. We hypothesized that dysregulated expression of HOX genes was associated with tumor development and malignant progression such as invasion and metastasis. In this study, we analyzed the expression patterns of 39 HOX genes in human invasive ductal breast cancer tissues and normal tissues by the real-time RT-PCR method. We found 11 HOX genes (HOXA1, A2, A3, A5, A9, C11, D3, D4, D8, D9 and D10) expression levels of which were significantly different between cancerous and normal tissues. All 10 genes except HOXC11 were expressed at lower levels in cancerous tissues than normal tissues. Comparing expression levels of each HOX gene among the different types of cancer tissues, the expression level of HOXB7 was lower in lymph node metastasis-positive cancer tissues than negative cancer tissues; those of HOXD12 and D13 were higher in progesterone receptor-positive cancer tissues than negative cancer tissues; and the expression level of HOXC5 was lower in cancerous tissues with mutated-type p53 than in normal and cancerous tissues with wild-type p53. These results suggest that the aberrant expression of HOX genes is related to the development of breast cancer and malignant behavior of cancer cells.

Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data.

OBJECTIVE: To better understand the nature of the malignancy of biliary tract carcinoma and evaluate the feasibility of its prediction by gene expression profiles. METHODS AND RESULTS: We explored the gene expression profiles characteristic of progression and invasiveness in the cDNA array data obtained from 37 biliary tract carcinomas (15 bile duct, 11 gallbladder, 11 of ampulla of Vater). We pre-selected 51 and 100 genes for the presence versus absence of lymph node metastasis and perineural invasion on the basis of statistical difference. To search optimized sets of genes for prediction, we applied a sequential forward feature selection, minimizing leave-one-out error rates on a k-nearest neighbor classifier. We could predict lymph node metastasis and perineural invasion with an accuracy of 94 and 100%, respectively. When the 6-stage IA cancers without perineural invasion were precluded, a marked difference in gene expression (147 gene), discriminable with 100% accuracy, was noted between positive versus negative perineural invasion, suggesting that the acquisition of invasive character is rather a later molecular pathological event in biliary tract cancer. CONCLUSION: The present method provides a powerful means of classifying biliary tract carcinomas. We also suggest that perineural invasion is an important target of array databased pattern classification, which may predict patient outcomes and facilitate the determination of the extent of surgery to minimize the risk of recurrence.

Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death in the world. Lymph node metastasis is not only an important factor in estimating the extent and the metastatic potential of an NSCLC but also in prognosticating the patient outcome. Preoperative prediction of lymph node metastasis might greatly facilitate the choice of appropriate surgical and medical options in patients with NSCLC. METHODS AND RESULTS: Using a cDNA array, we analyzed the expression profiles of 1,289 genes in 92 cancer tissues of NSCLC (37 squamous cell carcinomas and 55 adenocarcinomas). We divided the patients into two groups (classes) for each of various pathological factors, such as lymph node metastasis and pT-stage. For each pair of classes, we searched for an optimal combination of genes to classify the cases using a sequential forward selection algorithm starting from a gene set that showed significant difference in expression between the classes. We used the leave-one-out error cross-validation on a k-nearest neighbor classifier to sequentially choose the gene. Using the optimized set of genes, it was possible to stratify the patients for lymph node metastasis (pN-stage) and pT-stage at, respectively, 100% (23 genes) and 100% (55 genes) for cases with squamous cell carcinomas and 94% (43 genes) and 92% (35 genes) for those with adenocarcinomas. CONCLUSION: We conclude that expression profiling using feature selection provides a powerful means of stratification (personalization) of NSCLC patients and choice in treatment options, particularly for factors such as lymph node metastasis whose radiological diagnosis is presently incomplete.