Distinct Histological Types Research Articles

Clear cell renal cell carcinoma and papillary renal cell carcinoma: differentiation of distinct histological types with multiphase CT

Conventional clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) have different behavioral characteristics and clinical management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and evaluate its possible diagnostic role for preoperative differentiation using a standardized protocol. Quadriphasic multidetector computed tomography (CT) images (unenhanced, corticomedullary, nephrographic, and excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC lesions (mean ages, 62.3±14.1 and 61.4±13.7 years, respectively) were reviewed retrospectively. The attenuation characteristics were compared with the attenuation of the normal renal cortex using either multiple 10 mm2 regions of interest or whole tumor attenuation measurements. The degree of contrast enhancement was also compared. Univariate analysis revealed that ccRCC lesions showed higher mean attenuation values on the corticomedullary and nephrographic phases compared with pRCC masses (P < 0.05) using both measurement techniques. The findings underscore the importance of multiphase CT in the differentiation of these two subtypes of RCC using standard assessment techniques. The measurement of the degree of enhancement on contrast-enhanced multidetector CT may be a simple and useful method to radiologically differentiate between the two histological types of RCC.

Cancer stem cells markers CD44, CD24 and ALDH1 in breast cancer special histological types

AimsCD44, CD24 and ALDH1 are the most consistently used biomarkers to identify and characterise the breast cancer stem cell (CSC) phenotype. However, most studies performed until now analysed samples of...

MRI of Pediatric Patients: Part 1, Normal and Abnormal Cartilage

Cartilage development has a profound impact on musculoskeletal growth. The objective of this article is to offer insights about the maturation of hyaline cartilage through MRI. We begin by briefly describing the molecular make up of hyaline cartilage. We will then follow with a discussion of the basic principles to apply to optimize hyaline cartilage imaging. The remainder of the article will focus on the MR appearances of the distinct histologic types of hyaline cartilage, normal variations in cartilage development, and the sequelae of cartilage injury on normal skeletal development. Knowledge of the normal and abnormal appearances of hyaline cartilage on MRI of pediatric patients will allow readers to avoid mistaking the changes associated with skeletal maturation for pathologic findings.

The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer

Esophageal cancer (EC) is one of the most aggressive malignant tumors of the gastrointestinal tract. There are two distinct histological types of EC: esophageal squamous cell carcinoma and adenocarcinoma of the esophagus. Etiologic factors and the patterns of incidence of both subtypes are different. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in esophageal carcinogenesis. Gellatinases MMP-2 and MMP-9 are able to degrade collagen IV from basement membranes and extracellular matrix which is related to tumor progression, including invasion, metastasis, growth and angiogenesis. It has been shown that increased expression of MMPs plays a crucial role in the development of several human malignancies, including esophageal cancer. The activity of MMPs is regulated by their endogenous natural inhibitors (TIMPs). Among these, the roles of TIMP-1 and TIMP-2 in EC development, tumor progression and formation of metastases have been most extensively characterized and best recognized.

The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer.

Esophageal cancer (EC) is one of the most aggressive malignant tumors of the gastrointestinal tract. There are two distinct histological types of EC: esophageal squamous cell carcinoma and adenocarcinoma of the esophagus. Etiologic factors and the patterns of incidence of both subtypes are different. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in esophageal carcinogenesis. Gellatinases MMP-2 and MMP-9 are able to degrade collagen IV from basement membranes and extracellular matrix which is related to tumor progression, including invasion, metastasis, growth and angiogenesis. It has been shown that increased expression of MMPs plays a crucial role in the development of several human malignancies, including esophageal cancer. The activity of MMPs is regulated by their endogenous natural inhibitors (TIMPs). Among these, the roles of TIMP-1 and TIMP-2 in EC development, tumor progression and formation of metastases have been most extensively characterized and best recognized.

Molecular heterogeneity of triple-negative breast cancer and its clinical implications

Triple-negative breast cancer (TNBC) is defined by a lack of expression of hormone receptors, oestrogen and progesterone, as well as human epidermal factor receptor 2. This review focuses on the increasing understanding of the molecular heterogeneity of TNBC subtypes and the therapeutic implications of this subclassification. Emerging evidence clearly indicates that TNBC is a heterogeneous disease with varying prognosis according to clinical, pathological and genetic factors. Some distinct histological special types within this clinically defined collection of entities have been shown to have a particularly good prognosis (e.g. medullary carcinomas), and others very poor outcome (e.g. metaplastic carcinomas), whereas the broader immunohistochemically defined 'core-basal-like' or gene expression defined 'basal' groups generally have a poor prognosis. This molecular subclassification has implicated several biological processes as potential therapeutic targets: the DNA damage response, drivers of deregulated proliferation, angiogenesis, epithelial-mesenchymal transition and immune deregulation. Molecular stratification of these prognostic groups has been critical in identifying novel therapeutic targets for future drug development. The development of poly-(ADP)ribose polymerase inhibitors for BRCA1-mutation carriers with TNBC has led the ongoing efforts to translate fundamental biological insights into improved therapies for a difficult-to-treat breast cancer subgroup.

Abstract 1602: Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through a combination of defined genetic modifications and tumor microenvironment

Abstract Epithelial ovarian cancer includes several distinct histologic types including serous, mucinous, endometrioid, and clear cell. The cell origin of these distinct epithelial ovarian cancers has been debated for many years. Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbrial end of distal fallopian tube, although direct experimental evidence supporting this hypothesis is still lacking. To test this hypothesis, we immortalized a normal human fallopian tubal epithelial (FTE) cell line by using a retrovirus-mediated infection expressing the early region of SV40 T/t antigen and the human telomerase reverse transcriptase. These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence assay and inoculation into nude mice via subcutaneous or intraperitoneal injections. As expected, the HRASV12-transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, while no tumor growth was observed in immortalized FTEs. To our surprise, however, while histopathologic examination of resulting tumor from subcutaneous injections revealed a largely undifferentiated carcinoma with focal mucin production, tumors from intraperitoneal injections showed mucinous adenocarcinoma with rich mucin production from an undifferentiated area. The mucinous differentiation of tumors was most prominent near the peritoneal fat and other peritoneal organs including the pancreas, spleen, and intestine. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and CA125. Our study demonstrates that FTEs can generate mucinous adenocarcinoma through genetic modifications and that such mucinous differentiation is dependent on the peritoneal microenvironment. Thus, the experiment described here provided the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma, a distinct histologic entity of epithelial ovarian cancers whose origin is largely unknown. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1602. doi:10.1158/1538-7445.AM2011-1602

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ

To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(-) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(-)/PgR(-). Most type A were bcl-2(+)/p53(-) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(-)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.

The gene-reduction effect of chromosomal losses detected in gastric cancers

BackgroundThe level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.MethodsThe pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).ResultsMost of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).ConclusionsThe cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.

Simultaneous Renal Tumors with Distinct Histological Types in a 12-year-old Girl

Simultaneous Renal Tumors with Distinct Histological Types in a 12-year-old Girl

Abstract SY33-03: Role of telomerase in normal and neoplastic stem cells

Abstract We have used hTERT (the catalytic component of telomerase) to immortalize a variety of human cell types (sometimes in combination with Cdk4 to bypass cell culture stress). Cell types immortalized include skin keratinocytes and fibroblasts, muscle satellite cells, breast epithelial and stromal cells, corneal epithelial cells and fibroblasts (keratocytes), and human colonic epithelial cells. In addition, we have immortalized human bronchial epithelial cells (HBEC) and have determined that these cells can terminally differentiate into both central and peripheral lung cell types. These immortalized HBECs have been used to study the molecular pathogenesis of lung cancer by stable “knock down” of TP53 and also by over-expression of C-myc and mutant K-rasV12. When these cells containing multiple genetic alterations are introduced into immunosuppressed mice, the experimentally transformed cells make tumors that represent several distinct histological types. This suggests that these immortalized and transformed HBECs have bronchiolar-alveolar stem-like characteristics that can differentiate into multiple lineages. Stem cells are defined by both their ability to make more stem cells (self renewal) and their ability to produce cells that can differentiate. Experimentally immortalized human bronchial epithelial cells fulfill this definition of normal stem cells by continuous self renewal and by retaining the capability of differentiating into several cell types. Since experimentally transformed cells make lung tumors representing several major lineages, this is also an indication that the HBECs are derived from a multi-potent lung stem cell. Similar to normal stem cells, cancer (initiating) stem cells also have the ability to self-renew as well as undergo differentiation to give rise to phenotypically diverse types of cancer cells. There is mounting evidence that these rare cancer stem cells may be multidrug resistant and responsible for tumor relapse and metastasis. Targeted cancer therapeutic approaches seek to identify pathways that are more tumor specific, resulting in fewer side-effects and that may produce long-term durable responses. Telomerase is a novel cancer therapeutic target since it is activated in the vast majority of human cancers and telomeres of almost all human tumor cells are maintained at short but stable lengths. In addition, telomerase is not expressed or is expressed at levels that do not fully maintain telomeres in normal tissues, and telomeres are generally longer in normal stem cells compared to cancer cells. This potentially provides a therapeutic advantage for targeting telomerase over approaches that affect both normal and cancer cells equally. We have previously reported that telomerase positive cancer cells that are experimentally induced to undergo quiescence, down regulate telomerase. As part of our anti-telomerase therapeutics program, we have addressed the following questions: Are putative cancer stem cell populations quiescent and do they have short or long telomeres? While the molecular characteristics of cancer stem cells are not completely defined and subject to some controversies, we have isolated and examined cells expressing these cancer stem cell putative markers reported for breast, brain, prostate, pancreas, and lung cancer. In each case we have observed that purified cancer stem cell populations are positive for telomerase activity, indicating they are not quiescent. In addition, a telomerase inhibitor currently being tested in clinical trials robustly inhibits the activity of telomerase in these sorted sub-populations of putative cancer stem cells as well as the mass population of cancer cells. Finally, we have observed that cancer stem cells have short telomeres in comparison to normal stem cells. These findings support the idea that there may be a therapeutic window of opportunity to target cancer stem cells by inhibiting telomerase, thus driving telomeres progressively shorter leading to cancer stem cell death, potentially without irreversible damage to normal stem cells. Cancer remains a major cause of death in spite of substantial progress towards understanding the molecular basis of many types of cancers. The discovery of new drugs is a high priority, and telomerase inhibitors have the potential to act by a novel mechanism that will provide new options for cancer therapy. A review of ongoing anti-telomerase clinical trials will be presented. In summary, telomerase inhibitors might not only directly limit or stop the growth of human tumors including cancer stem cells, but might also act in an additive or synergistic fashion with existing therapies to amplify their effectiveness. Citation Format: Jerry W. Shay. Role of telomerase in normal and neoplastic stem cells [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY33-03

Correlation Between Argyrophilic Nucleolar Organizer Region Staining and Brain Tumor Classification and Grading

ABSTRACTDistinctions between benign and malignant tumors are less evident in the central nervous system than in other tissues. Since the level of cell proliferation is an important feature in tumor grading, we applied AgNOR in 50 cases of brain tumors with different grades and histological origins in order to check its efficiency in discriminating between benign and malignant cases. We found significant differences between the means of grade I (1.76) and grade IV (2.46) tumors. No significant differences were observed considering the same grading with distinct histological types or age of patients, reinforcing the efficiency of AgNOR.

Management and Surgical Resection for Tumors of the Trachea and Carina: Experience with 32 Patients

The purpose of the present study was to investigate the complications, long-term survival, and management lessons learned after surgical resection for patients with primary tumors of the trachea and carina and locally advanced lung cancer directly infiltrating the carina. A retrospective study was performed by our department on 32 patients undergoing surgical resection for primary tumors of the trachea and carina and locally advanced lung cancer directly infiltrating the carina between June 1986 and June 2003. Various surgical modalities were performed according to the tumor location and extent: tracheal resection in 10 cases, carinal resection and reconstruction in 4 cases, carinal right upper lobectomy in 8 cases, carinal pneumonectomy in 4 cases, and partial tangential resection of the tracheal wall in 6 cases. Cardiopulmonary bypass was required in two patients for nearly complete obstruction of the trachea. Resected tumors included six distinct histologic types. Perioperative mortality was 9.4% (3/32). Major complications occurred in 31.3% (10/32) of the patients. The overall 1-, 3-, and 5-year survival rates were 87.5%, 56.3%, and 40.6%, respectively. Patients with primary tracheal and carinal tumors experienced a 5-year survival of 55.0% compared to 16.7% for those with locally advanced lung cancer directly infiltrating the carina (P < 0.05). Surgical resection is the most effective treatment of choice for primary tumors of the trachea and carina. With careful patient selection and meticulous surgical and anesthesia techniques, the operative mortality and complications are acceptable, and long-term survival can be achieved.

Smooth muscle tumor of the placenta - an entrapped maternal leiomyoma: a case report

IntroductionNeoplasms of the placenta are uncommon. Tumors arising from the placental tissue include two distinct histological types: the benign vascular tumor, chorangioma, and very rarely, choriocarcinoma. Benign leiomyomas, in contrast, are very common tumors of the uterine wall and occur in 0.1% to 12.5% of all pregnant women. However, the incorporation of uterine leiomyoma into the placenta is exceptional and raises the question of its origin. This case is possibly the first report on this kind of a placental tumor which has been examined using both immunohistochemistry and chromosome analysis.Case presentationA 34-year-old G4P3 Caucasian woman was followed up antenatally because of a stillbirth in her previous pregnancy. At 36 weeks' gestation, a hypoechoic, 3.6 × 4.2 cm rounded mass was noted within the placenta on ultrasound examination. Histologically, the tumor was a benign leiomyoma and this finding was supported by immunohistochemistry. The newborn infant was male. Chromosomes of the neoplasm were studied by the fluorescence in situ hybridization technique and the tumor was found to carry XX chromosomes.ConclusionA rare benign smooth muscle neoplasm involving the placental parenchyma is presented. The tumor was a uterine leiomyoma of maternal origin, which had become entrapped by the placenta. This case report is of interest to the clinical specialty of obstetrics and gynecology and will advance our knowledge of the etiology of placental tumors.

Expression and Clinical Significance of Focal Adhesion Kinase in the Two Distinct Histological Types, Intestinal and Diffuse, of Human Gastric Adenocarcinoma

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression and metastasis. The aim of this study was to assess the clinical significance of FAK expression in the two distinct histological types of human gastric neoplasia. FAK expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma cases, 30 intestinal and 36 diffuse type, and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival. In intestinal type carcinomas, enhanced FAK expression was significantly associated with increased tumor proliferative capacity (P = 0.012). In diffuse type carcinomas, FAK staining intensity was significantly correlated with tumor size (P = 0.026) and disease stage (P = 0.024), presenting also a borderline association with nodal status (P = 0.053). In diffuse type carcinomas, enhanced FAK expression was significantly associated with longer overall survival times (log-rank test, P = 0.014), being also identified as an independent prognostic factor in multivariate analysis (Cox regression, P = 0.016). In contrast, patients with intestinal type tumors and enhanced FAK expression were characterized by shorter overall survival times, without though reaching statistical significance (log-rank test, P = 0.092). The current data support evidence that FAK protein may be considered as a diagnostic and prognostic marker in gastric neoplasia. Further studies conducted on larger clinical samples and highlighting on the distinct impact of the two histological types are warranted to delineate the clinical significance of FAK protein in gastric neoplasia.

Frequent Alterations of p16INK4a and p14ARF in Oral Proliferative Verrucous Leukoplakia

Proliferative verrucous leukoplakia (PVL) represents a rare but highly aggressive form of oral leukoplakia with > 70% progressing to malignancy. Yet, PVL remains biologically and genetically poorly understood. This study evaluated the cell cycle regulatory genes, p16INK4a and p14ARF, for homozygous deletion, loss of heterozygosity, and mutation events in 20 PVL cases. Deletion of exon 1beta, 1alpha, or 2 was detected in 40%, 35%, and 0% of patients, respectively. Deletions of exons 1alpha and 1beta markedly exceed levels reported in non-PVL dysplasias and approximate or exceed levels reported in oral squamous cell carcinomas. Allelic imbalance was assessed for markers reported to be highly polymorphic in squamous cell carcinomas and in oral dysplasias. Loss of heterozygosity was detected in 35.3%, 26.3%, and 45.5% of PVLs for the markers IFNalpha, D9S1748, and D9S171, respectively. INK4a and ARF sequence alterations were detected in 20% and 10% of PVL lesions, accordingly. These data show, for the first time, that both p16INK4a and p14ARF aberrations are common in oral verrucous leukoplakia; however, the mode and incidence of inactivation events differ considerably from those reported in non-PVL oral premalignancy. Specifically, concomitant loss of p16INK4a and p14ARF occurred in 45% of PVL patients greatly exceeding loss reported in non-PVL dysplastic oral epithelium (15%). In addition, p14ARF exon 1beta deletions were highly elevated in PVLs compared with non-PVL dysplasias. These data illustrate that molecular alterations, even within a specific genetic region, are associated with distinct histologic types of oral premalignancy, which may affect disease progression, treatment strategies, and ultimately patient prognosis.

Molecular targets and biological modifiers in gastric cancer

The overall survival of gastric cancer patients remains poor despite efforts and advances in its prevention, diagnosis, and treatment. The development of new therapies is crucial for the effective control of this disease. An increasing number of genetic and epigenetic alterations have been associated with distinct histological types of gastric cancer. In this review, we will discuss the involvement of E-cadherin, EGFR, ERBB2, MMR genes, KRAS, and PIK3CA in the development and progression of gastric cancer and their role as biomarkers or as novel putative targets for therapy.

Immunohistochemical and ultrastructural characterization of brain tumors in S100β‐v‐erbB transgenic rats

Transgenic rats expressing v-erbB (viral form of the EGF receptor) under transcriptional regulation by the S100beta promoter develop brain tumors (Ohgaki et al. J Neuropathol Experimental Neurol 65: 1111-1117, 2006). In the present study, we carried out detailed immunohistochemical and ultrastructural characterization of the brain tumors that developed in these rats. Of 49 homozygous transgenic rats between 16 and 94 weeks of age (mean, 59 weeks), 31 rats were autopsied because they showed severe neurological symptoms and/or became moribund. Among these, 30 rats had brain tumors, which were classified histologically as malignant glioma, anaplastic oligodendroglioma, and low-grade oligodendroglioma. Six transgenic rats developed two different histologic types of brain tumor, which were considered to be of multiclonal origin, because of the lack of histological transitions. All brain tumors contained neoplastic cells immunoreactive for S100 and GFAP. Diffuse immunoreactivity for Olig2 and Nkx2.2 was observed in neoplastic cells in all seven anaplastic oligodendrogliomas and in all three low-grade oligodendrogliomas analyzed, but in none of 26 malignant gliomas. Electron microscopy, carried out on four malignant gliomas and four anaplastic oligodendrogliomas, revealed the presence of intermediate filament bundles devoid of side arms, indicating glial differentiation. There was no evidence of cilia, microvilli, neurosecretory granules, synaptic structures or neurofilaments, excluding the possibility of ependymal or neuronal tumors. The present study thus provides additional evidence that the brain tumors developing in S100beta-v-erbB transgenic rats are of glial origin, with or without oligodendroglial differentiation. Reproducible development of three distinct histologic types of brain tumor in unique localizations may be explained by activation of the v-erbB transgene driven by the S100beta promoter in specific precursor cells during development of the brain. Thus, S100beta-v-erbB transgenic rats may be useful to study the histogenesis and molecular mechanisms of development of glial tumors due to disruption of the EGFR pathway.

Betaig-h3 Tumor Suppressor Gene Expression is Absent in Human Low-grade Follicular Lymphoma but not in High-grade Follicular Lymphoma

The Betaig-h3 gene encodes a secreted protein that appears to be involved in tumor invasion by mediating cellular adhesion/migration throughout the extracellular matrix. Indeed, it has been previously demonstrated that the Betaig-h3 gene has tumor suppressor function, and the gene's expression is downregulated in human tumor cell lines of distinct histological types (including lymphoreticular) but is intact in their non-cancerous counterparts. Knock-out mice lacking Betaig-h3 expression have a high incidence of malignant tumor formation (43%, vs.

2007 Annual Meeting of the National Lung Cancer Partnership: A Summary of Meeting Highlights

This report presents highlights from The National Lung Cancer Partnership's Annual Meeting, held in June 2007 in Chicago. It discusses recent refinements in the histologic, genetic, and epigenetic subtyping of lung cancers and suggests reasons why certain therapies benefit only a subset of lung cancer patients. It also describes new molecular data about the subtype-specific differences in drug resistance among bronchioloalveolar-associated non-small cell lung cancers and discusses strategies to avoid or tackle specific drug-resistant tumors. Finally, it describes new findings about epigenetic differences-specifically in DNA hypermethylation-among lung tumors, including some male/female differences, which may prove useful as biomarkers for diagnosis, prognosis, and prediction of response to treatments.