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BACKGROUND This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients. METHODS A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression. RESULTS Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis-prediction model, we categorized patients into low, intermediate, and high-risk groups, which had greater accuracy in predictive ability (log-rank statistics = 54.66) than the conventional tumor node metastasis staging (log-rank statistics = 39.56). Next, we generated a prognosis-prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high-risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy. CONCLUSIONS This prognosis-prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

Background and Objectives There is still little evidence of a relationship between pathologic stage with or without preoperative chemoradiotherapy (CRT) in rectal cancer. The aim of this study was to investigate the prognostic implication of the preoperative-CRT pathologic stage (ypStage) by comparing it to the pathologic stage without preoperative-CRT (pStage). Methods Between July 2004 and December 2012, 774 consecutive patients who received radical surgery for histologically diagnosed rectal adenocarcinoma (clinical stage I–III) were included. Results A total of 674 surviving patients were followed-up for a median of 43.4 months. Five-year local recurrence (LR) -free survival rates were similar for each ypStage and the corresponding pStage. In contrast, 5-year distant metastasis (DM) -free survival rates were poorer for each ypStage than for the corresponding pStage. The hazard ratio increased with a decrease in pathological stages (Stage I: 3.5, Stage II: 2.2, and Stage III: 1.4). Conclusions ypStage in rectal cancer is a good prognostic factor in predicting LR and DM. Although the ypStage can stratify patients according to the risk of developing DM, the risk as determined by the ypStage could be higher than that of corresponding pStage, especially in patients showing a higher degree of downstaging. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Background The purpose of the present study was to assess the value of matrix metalloproteinase (MMP)-2 and MMP-9 expression and other potential prognostic factors in predicting the clinical outcome of patients after definitive surgery for pathologic stage IA non-small cell lung cancer (NSCLC). Methods One hundred and forty-six consecutive and non-selected patients who underwent definitive surgery for stage IA NSCLC were included in this study. Formalin-fixed paraffin-embedded specimens were stained for MMP-2 and MMP-9, which were statistically evaluated for their prognostic value and other clinicopathological parameters. Results Of the 146 patients studied, 102 (69.9%) cases were classified as having high expression for MMP-2. A total of 89 carcinomas (61.0%) had high expression for MMP-9. MMP-9 expression correlated with Eastern Cooperative Oncology Group (ECOG) performance status, pT stage, and differentiation (P = 0.005

BACKGROUND Studies of prostate cancer microvessels to date have relied on routine two-dimensional images from histologic tissue sections, and there have been no previous reports of three-dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two-dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated. METHODS We developed a novel method to visualize and analyze prostate microvessels in three dimensions from serially-sectioned prostate specimens, including tissue preparation, reconstruction of serial histologic sections into 3D volumes, extraction of vessels from this data set, and calculation of geometric characteristics. Eleven regions of benign and cancer tissue were studied and compared in an effort to validate our methodology. RESULTS Microvessels and glandular elements from benign and malignant tissue were visualized together in three dimensions. In the 3D visualizations, microvessels associated with cancer were seen to have more arbitrary pathways, increased tortuosity, and a more casual relationship with glandular elements than microvessels associated with benign tissue. A quantitative measure, the volume length density, discriminated between benign tissue and cancer better than simple microvessel density in this exploratory study. CONCLUSIONS Microvessels in prostate cancer have a more homogeneous distribution and greater tortuosity than those in benign tissue. Volume length density of microvessels shows promise as a 3D marker in prostate cancer. Prostate 37:270–277, 1998. © 1998 Wiley-Liss, Inc.

Background: The purpose of this study was to determine the ability of clinical tests to predict advanced pathologic stage (seminal vesicle invasion, pT3c, or pelvic lymph node metastases, pN+). Methods: T stage, PSA, PSA density, and pathologic features in systematic biopsy specimens were correlated with pathologic stage in 190 consecutive patients with clinically localized (T1-3) prostate cancer detected by systematic needle biopsies and treated with radical prostatectomies. Results: Thirty-three patients (17%) had an advanced pathologic stage cancer (pT3c or pN+). In logistic regression analysis, the total length of cancer in all biopsy cores (P < 0.0005), the percent of poorly-differentiated cancer in each specimen (P < 0.021), and serum PSA (P < 0.028) were the only significant predictors of advanced stage. A model was constructed to predict advanced stage: if the PSA was 6 ng/mL and 4 or more biopsy cores were positive and the total length of cancer in all cores was 20 mm and at least 10% of the cancer was poorly-differentiated, then 14 (93%) of 15 patients had an advanced pathologic stage cancer compared to 11% of the remaining 175 patients (P < 0.0005). Conclusion: The pathologic features of cancer in systematic needle biopsy specimens more accurately predicts which patients have advanced stage cancer than standard clinical tests alone.

Previous studies of prostatic duct adenocarcinoma have reported a poor prognosis, but they included few patients treated by radical prostatectomy. The authors studied 15 cases treated with radical prostatectomy to define more completely their pathologic features and determine the clinical outcome in these surgically treated patients. The study included morphometry and DNA image analysis using the CAS-200 system. The most common presentation was urinary outlet obstruction (n = 9), and most patients were clinical Stage B with palpable prostatic lesions (n = 12). Compared with acinar cancers of similar clinical stage, duct cancers were large (tumor volume, 8.4 +/- 10.0 cc) and occupied a large portion of the gland (23 +/- 21%). Duct cancers were in an advanced final pathologic stage with 93% having capsular penetration, 47% positive margins, 40% seminal vesicle invasion, and 27% positive pelvic lymph nodes. The DNA analysis on cells disaggregated from paraffin revealed that 54% of cases were diploid, 15% tetraploid, 8% aneuploid, and 23% tetraploid/aneuploid. On clinical follow-up, eight patients had no evidence of tumor at intervals ranging from 1 to 28 months, and seven patients (47%) had persistent tumor at intervals of 3 to 18 months. This study demonstrates that duct cancers are in an advanced pathologic stage by the time of presentation and have a much higher short-term failure rate after radical prostatectomy compared with acinar cancers.

Transurethral resections (TUR) and totally embedded radical prostatectomies from 39 clinical Stage A2 prostate cancers were morphometrically analyzed and compared with 56 prior similarly studied clinical Stage B cancers. All the clinical A2 radical prostatectomies contained residual tumor with 26% having capsular penetration. Clinical Stage A2 tumors were much more heterogeneous than clinical Stage B tumors with respect to tumor location, grade, and amount. In particular, many clinical A2 cases were predominantly central or central and anterior in location (59%) and low-grade compared with clinical Stage B cases where most lesions were posterior, peripheral, and intermediate grade. Percent of tumor in TUR best predicted final pathologic stage versus TUR grade or volume. Despite statistically significant correlations between tumor percent and/or grade on TUR and final stage, predictability of final stage for individual patients from TUR data was poor. The complex interrelation of tumor location, grade, and amount resulted in wide and overlapping ranges for these parameters for organ-confined and nonconfined cases.

Data from 996 newly diagnosed breast cancer patients indicated a highly significant association (P less than 0.001) between periodic breast self-examination (BSE) and pathologic stage of disease. Among women reporting periodic BSE, only small differences were noted between those who practiced monthly and those who practiced several times annually. Average maximum tumor diameter and frequency of tumors 4 cm or large were significantly greater (P less than 0.01) among women who rarely or never practiced BSE. The relationship between the periodic practice of BSE and the diagnosis of breast cancer before nodal involvement was present even after controlling for a wide variety of variables. The regular practice of BSE was associated with a one-third reduction in the likelihood of diagnosis of disease with positive nodes. This difference translated to a 10% decline in five-year mortality for whites and a 17% decline for nonwhites.

Many investigators have regarded Stage III lymphomas as a generalized form of disease and have accordingly recommended systemic treatment programs. Between 1961 and 1973, 68 patients with clinical or pathologic Stage III non-Hodgkin's lymphomas were seen in the Division of Radiation Therapy at Stanford University Medical Center and were treated by high dose (3500 rads or more) total lymphoid radiation therapy only. Of the 17 patients who had a diffuse histologic pattern, the actuarial survival at 5 years was 39%, but only three patients have remained free of disease. In contrast, for the 51 patients who had a nodular histologic pattern, the actuarial survivals at 5 and 10 years were 75% and 65%, respectively. Corresponding relapse-free survivals for patients with nodular lymphomas were 43% and 33%, respectively. Of 28 patients who relapsed with nodular lymphomas, 18 (64%) had relapses confined to lymph nodes; six of these were extensions to previously unirradiated epitrochlear-brachial nodes. Seven of the 18 patients were treated only with further conventional external radiation therapy at the time of their relapses and remain free of disease for additional periods of 2 to 5 years. Hence, 30 of 51 (59%) patients with nodular lymphomas have thus far been controlled by high dose total lymphoid irradiation only. Over 90% of relapses among patients with nodular lymphomas were seen within the first 5 years. The data suggest that high dose conventional radiation therapy to incorporate not only the routine total lymphoid fields but also the epitrochlear, mesenteric, and Waldeyer's ring region has curative potential even in Stage III non-Hodgkin's lymphomas, especially in the nodular group.

The thymidine labeling index (TLI) was measured in vitro in 278 primary breast carcinomas. In 227 operable women treated by radical mastectomy, TLI's below the median of 4.55% carried a probability of relapse of 20% at four years, in contrast to 52% for TLI's above the median (P = 0.0001). The probability of relapse was significantly related to the TLI independent of TNM pathologic stage, axillary lymph nodal status alone, estrogen receptor (ER) content, or menopausal status. The abilities of the TLI and nodal status to predict early relapse were equally strong and independent, whereas other variables tested had less or no independent predictive capacity. The predictive value of the ER content depended largely on its relationship to the TLI, and ER was related to the probability of relapse in the below median TLI group only. The TLI can select a subgroup of node-negative patients with a relapse-expectancy of approximately 50% at four years.

One hundred fourteen cases of bladder cancers treated during a 3-year period by cystectomy were uniformly reclassified, graded, and pathologically staged. One hundred thirty-one cases treated during the same period by transurethral or segmental resection were similarly reclassified and checked for muscle invasion. Sixty-one percent of the cystectomy cases were nonpapillary and 69% of the conservatively treated cases were papillary transitional cell carcinomas. In the pathologically staged cystectomy group, all poorly differentiated (grade III and IV) carcinomas were invasive. Nonpapillary tumors were more aggressive and 79% of the high grade tumors in these categories extended into the outer portions of the muscularis or into perivesical tissues. Muscle invasion could also be demonstrated in 74% of the 23 high-grade nonpapillary carcinomas in the conservatively treated cases. Lymph node and pelvic wall metastases were found in 17% of the cystectomies and were present only in tumor grades III and IV and a pathologic stage of P-3B or higher. None of the well differentiated (grade I) papillary carcinomas were invasive and invasion was superficial in most moderately differentiated (grade II) papillary tumors. The findings confirm that pathologic classification and grading of bladder carcinomas correlate closely with the stage of the disease.

The common clinical staging techniques for nonseminomatous testicular cancer fail to predict the pathologic stage in a significant number of patients with Stages I, IIS, and IIA disease. Newer techniques such as ultrasonography and computed tomography are useful in more advanced disease (Stages IIB or higher), but neither can detect microscopic metastases (Stage IIA). The accuracy of clinical staging may be improved by the discovery of new tumor markers and the devising of assays for tumor-associated antigens, but at present retroperitoneal lymphadenectomy is needed for staging as well as for treatment.

The distributional patterns of blood group substance H and carcinoembryonic antigen (CEA) in 20 colorectal carcinomas from 17 patients, were investigated. Prognosis in these cases was more obviously related to histologic classification and pathologic stage than to BGS and CEA distributional patterns or preoperative plasma CEA levels. The distribution of H and CEA was similar to that found by other investigators for A and B blood group substances with the exception that areas of identical localization could be shown in at least some areas of each tumor studied that was positive for both antigens. The relationship of CEA and BGS is as yet unknown, but it seems probable that they can occur simultaneously in the same tissue.

One hundred eighty-seven patients with confirmed diffuse non-Hodgkin's lymphoma were selected from a consecutive series of 391 patients who were evaluated and treated at Stanford University Medical Center. Lymphomas with any degree of nodularity and diffuse lymphomas of "well-differentiated" and "poorly differentiated" lymphocytic type were excluded from this study. Each of four observers identified cases of diffuse large-cell lymphoma from the 187 cases and further subdivided these cases into six morphologic types in accordance with criteria proposed by Strauchen et al. Initial intraobserver and interobserver agreement was relatively low but was greatly enhanced when the initial six morphologic types were grouped as either follicular center-cell or nonfollicular center-cell types. When individual observer results were pooled, statistically significant differences were seen between survival of patients in these two groups, with the patients in the nonfollicular differences were seen between survival of patients in these two groups, with the patients in the nonfollicular center-cell group having a worse prognosis (P = 0.04). This effect of morphologic type appeared to be independent of pathologic stage. Mitotic counts did not correlate with survival.

One-hundred-sixty-nine lung cancers have occurred to date among 10,040 cigarette smoking men who participated in the New York Lung Cancer Detection Program. Almost 40% of the cases, 65, were still Stage I when their disease was diagnosed; 62 had thoracotomy and resection, and in 57, mediastinal node dissection confirmed that the mediastinum was free of metastases ("true pathologic" Stage I). Fifty-four of the 62 (87%) are still alive at this time, while only 15 of 104 (14%) of those with Stage II and III lung cancers are alive. Only two patients of the 62 in Stage I who were treated by resection died of lung cancer, both with T2 tumors. Two others are alive with metastases, one died postoperatively, and five died of other causes without evidence of lung cancer. The estimated probability of survival for true Stage I lung cancer is over 90% at five years, and close to 40% of all lung cancers can be detected in this favorable stage by present radiologic and cytologic screening techniques.

Treatment of the regional lymph nodes forms an integral part of the management of any patient with carcinoma of the tongue. It is the most important determinant of survival. Although survival correlates with the size of the primary tumor, it may also be explained by the higher incidence of metastatic nodes in larger lesions. The incidence of contralateral neck nodes is high, and treatment of the contralateral neck, even in smaller carcinomas of the tongue, must be considered. Anterior tongue carcinomas are equally as aggressive as posterior carcinomas of the tongue. An analysis of the cause of failure following treatment of tongue carcinomas emphasizes the fact that too many clinical stages I and II cancers--those with clinically negative neck examination--are in fact pathologic stage III cancers.

The records of 25 patients with unresectable carcinoma of the rectum and rectosigmoid who received preoperative radiation therapy (RT) were reviewed. Twenty patients were considered to be resectable following RT (80%). Sixteen patients (64%) underwent curative resections. All patients with unresectable tumors following RT died with tumor within two and one half years (median survival, 11 months). For patients undergoing curative resection, the probability of two- and five-year survival was 56% and 43%, respectively. In this latter group, five of seven patients with treatment failures (71%) had a pelvic component of disease. The incidence of pelvic recurrence was correlated with the pathologic stage, extent of resection and preoperative radiation dose. The need for more aggressive treatment for patients with these advanced tumors is emphasized. Future treatment alternatives are discussed.

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to megavoltage radiotherapy alone and relatively resistant to combination chemotherapy.

Cutaneous malignant melanomas of the head and neck are prognostically engimatic. In addition to known prognostic determinants of stage and lesion microstage, lesion location also appears to have prognostic importance. The authors have reviewed a series of 83 microstaged head and neck melanoma patients in order to analyze the relative importance of these factors. There were 36 males and 47 females with a median age of 56 years. Eighty-one percent had pathologic Stage I disease, 7% were Stage II, and 12% were Stage III. The primary location was face in 32 patients, neck in 18, ear in 12, and scalp in 21 patients. The actuarial 5-year survival according to lesion thickness was 86% for melanoma less than 1.0 mm, 56% for 1 to 2 mm thick lesions, 47% for 2.1 to 4 mm thick lesions, and 25% for melanomas greater than 4.0 mm. The 5-year survival according to lesion location was 78% for facial and 58% for neck melanomas; for ear and scalp, the respective survivals were 33% and 37%. Median thickness was 2.0 mm for facial and 1.85 mm for neck lesions. It was 2.7 mm for ear and 2.0 mm for scalp lesions (differences not significant). There were no microstage factors that correlated with the adverse prognosis seen with scalp and ear melanomas. Multivariate analysis in the entire series (all clinical stages) showed the following to be significant: stage, thickness, and location of the primary melanoma (all less than 0.0002). In clinical Stage I melanoma, the significant prognostic factors were location (P = 0.035), thickness (P = 0.008), level (P = 0.024), and ulceration (P = 0.035). The prognosis of head and neck melanoma is uniquely influenced by location of the primary lesions in addition to stage, thickness, level, and ulceration, as observed with other cutaneous melanomas at other sites. Ear and scalp melanomas are high-risk lesions whose poor prognosis is not readily explained by any of the microstage factors reviewed.